bluuebunny/crossref_metadata_2025 huggingface dataset:
Renal and hemodynamic effects of intravenous fenoldopam versus nitroprusside in severe hypertension.
Authors: Elliott W J , Weber R R , Nelson K S , Oliner C M , Fumo M T , Gretler D D , McCray G R , Murphy M B
Published: June 2011

The renal and hemodynamic effects of intravenously administered fenoldopam mesylate, a novel dopamine-1 receptor agonist, were compared with those of sodium nitroprusside in 28 patients (18 male; 26 black, two white; average age, 49 +/- 3 years) with an average blood pressure of 219/137 mm Hg, most of whom presented with acute target organ damage. Fenoldopam and nitroprusside lowered blood pressure safely to an average pressure of 176/105 mm Hg; highly significant dose-response relations were found for the 13 patients receiving fenoldopam and the 15 receiving nitroprusside. Volume and sodium, potassium, and creatinine concentrations were measured in freely voided urine specimens both before and during intravenous therapy. In the fenoldopam-treated patients, there were significant increases in urinary flow (92 +/- 21 to 168 +/- 37 ml/hr, p less than 0.003), sodium excretion (227 +/- 73 to 335 +/- 90 mu eq/min, p less than 0.001), and creatinine clearance (70 +/- 11 to 93 +/- 13 ml/hr, p less than 0.003). In the nitroprusside-treated group, however, all these parameters decreased, but not significantly. For direct comparison of the two agents, the increments in urinary flow rate (+76 +/- 20 vs. -16 +/- 15 ml/hr, fenoldopam vs. nitroprusside), sodium excretion (+109 +/- 28 vs. -39 +/- 28 mu eq/min), and creatinine clearance (+23 +/- 6 vs. -11 +/- 7 ml/min) were significantly greater (p less than 0.001 for each) in the fenoldopam-treated group. Significant differences were also obtained when these parameters were calculated as percentage increase over baseline. Fenoldopam and nitroprusside are effective therapies for severe, accelerated, or malignant hypertension, but fenoldopam had additional salutary renal effects in these patients.
Low incidence of fatal coronary heart disease in Pima Indians despite high prevalence of non-insulin-dependent diabetes.
Authors: Nelson R G , Sievers M L , Knowler W C , Swinburn B A , Pettitt D J , Saad M F , Liebow I M , Howard B V , Bennett P H
Published: June 2011

The incidence of fatal coronary heart disease (CHD) was determined in a population of Pima Indians from the Gila River Indian Community in Arizona. Between 1975 and 1984, 394 deaths occurred among 4,828 subjects aged 5 years or older, and 199 of these occurred in the 1,093 persons with non-insulin-dependent diabetes. Only 28 deaths were attributed to CHD; all occurred among the 689 diabetic persons 45 years of age or older. No CHD deaths occurred among the 419 nondiabetic subjects 45 years of age or older. The rate of fatal CHD among the diabetic subjects was higher in men than in women and increased with advancing age and duration of diabetes. A higher incidence of fatal CHD was associated with proteinuria, renal insufficiency, medial arterial calcification, diabetic retinopathy, insulin therapy, and an abnormal electrocardiogram. In Pima Indians aged 50-79 years, the incidence of fatal CHD was less than half that found in the Framingham population after controlling for age, sex, and diabetes (incidence rate ratio, 0.4; 95% confidence interval, 0.2-0.7). Factors protecting Pima Indians from fatal CHD may include racial heritage, low serum concentrations of total and low density lipoprotein cholesterol, and rarity of heavy smoking. Among the diabetic subjects, mortality from diabetic renal disease, which shows many of the same risk factors, may selectively compete and remove those at risk for fatal CHD. This would not, however, explain the lack of fatal CHD among the nondiabetic subjects. Fatal CHD shares many of the risk factors associated with the specific microvascular complications of diabetes, and diabetes and its associated attributes are the major predictors of fatal CHD in this population.
Pertussis toxin treatment of whole blood. A novel approach to assess G protein function in congestive heart failure.
Authors: Maisel A S , Michel M C , Insel P A , Ennis C , Ziegler M G , Phillips C
Published: June 2011

This study was designed to assess G protein function in mononuclear leukocytes (MNL) of patients with congestive heart failure (CHF). MNL membranes were ADP-ribosylated in vitro in the presence of pertussis or cholera toxin. The amount of pertussis toxin substrates did not differ significantly between CHF patients (6,100 +/- 224 fmol/mg, n = 23) and age-matched healthy control subjects (5,812 +/- 972 fmol/mg protein, n = 19). Among the CHF patients, no differences were observed between those with idiopathic and ischemic CHF. The amount of cholera toxin substrates also did not differ significantly between CHF patients (7,522 +/- 1,405 fmol/mg protein, n = 11) and control subjects (5,654 +/- 707 fmol/mg protein, n = 14). Moreover, basal and isoproterenol- and prostaglandin E1-stimulated cyclic AMP (cAMP) accumulation in MNL was similar in control subjects and patients. To detect more subtle alterations of the cAMP-generating system, we incubated anticoagulated blood with 250-400 ng/ml pertussis toxin for 4 hours at 37 degrees C. This treatment completely ADP-ribosylated the MNL pertussis toxin substrates. Incubation with pertussis toxin did not change basal or prostaglandin E1-stimulated cAMP generation in MNL of control subjects, but it significantly enhanced stimulated generation (443 +/- 44 vs. 643 +/- 93 pmol/10(7) cells, p less than 0.025) in MNL of CHF patients. This enhancement was most pronounced in the most severely ill patients (New York Heart Association class IV) and correlated with plasma norepinephrine levels, another marker of CHF severity (r = 0.798, n = 11, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Detection of left main coronary artery stenosis by transesophageal color Doppler and two-dimensional echocardiography.
Authors: Yoshida K , Yoshikawa J , Hozumi T , Yamaura Y , Akasaka T , Fukaya T , Kato H
Published: June 2011

Although transthoracic two-dimensional echocardiography can detect dilation of the coronary arteries, the reliability of this technique in the detection of coronary artery stenosis is still doubtful. The purpose of this study was to test the ability of newly developed biplane transesophageal color Doppler and two-dimensional echocardiography in the detection of left main coronary artery stenosis. Blood flow in the left main coronary artery was detected in 57 of 67 (85%) patients by transesophageal color Doppler flow imaging. Using transesophageal two-dimensional echocardiography, adequate images of the full length of the left main coronary artery and identification of the bifurcation were obtained in 60 of 67 (90%) patients. Transesophageal echocardiography clearly showed significant (greater than or equal to 50%) narrowing of the coronary lumen in 10 of 11 patients (sensitivity, 91%) and insignificant narrowing or no abnormalities of the coronary lumen in the other 49 patients (specificity, 100%). The positive predictive accuracy for left main coronary artery disease was 100%, and the negative predictive accuracy was 98%. This preliminary study suggests that biplane transesophageal color Doppler and two-dimensional echocardiography appears to be a feasible noninvasive technique for imaging the left main coronary artery and detecting hemodynamically significant luminal obstruction.
Relation of pulmonary vein to mitral flow velocities by transesophageal Doppler echocardiography. Effect of different loading conditions.
Authors: Nishimura R A , Abel M D , Hatle L K , Tajik A J
Published: June 2011

It has previously been demonstrated that predictable changes occur in mitral flow velocities under different loading conditions. The purpose of this study was to relate changes in pulmonary venous and mitral flow velocities during different loading conditions as assessed by transesophageal echocardiography in the operating room. Nineteen patients had measurements of hemodynamics, that is, mitral and pulmonary vein flow velocities during the control situation, a decrease in preload by administration of nitroglycerin, an increase in preload by administration of fluids, and an increase in afterload by infusion of phenylephrine. There was a direct correlation between the changes in the mitral E velocity and the early peak diastolic velocity in the pulmonary vein curves (r = 0.61) as well as a direct correlation between the deceleration time of the mitral and pulmonary venous flow velocities in early diastole (r = 0.84). This indicates that diastolic flow velocity in the pulmonary vein is determined by the same factors that influence the mitral flow velocity curves. A decrease in preload caused a significant reduction in the initial E velocity and prolongation of deceleration time, and an increase in preload caused an increase in E velocity and shortening of deceleration time. An increase in afterload produced a variable effect on the initial E velocity and deceleration time and was dependent on the left ventricular filling pressure. The change in systolic forward flow velocity in the pulmonary vein was directly proportional to the change in cardiac output (r = 0.60). The pulmonary capillary wedge pressure correlated best with the flow velocity reversal in the pulmonary vein at atrial contraction (r = 0.81). Use of pulmonary vein velocities in conjunction with mitral flow velocities can help in understanding left ventricular filling.
Body fat distribution and male/female differences in lipids and lipoproteins.
Authors: Freedman D S , Jacobsen S J , Barboriak J J , Sobocinski K A , Anderson A J , Kissebah A H , Sasse E A , Gruchow H W
Published: June 2011

The role of body fat distribution, as assessed by the ratio of waist-to-hip circumferences (WHR), in statistically explaining differences in levels of lipoproteins between men and women was studied using data collected in 1985-1986 from employed adults (mean age, 40 years). As compared with the 415 women, the 709 men had higher mean levels of triglycerides (+38 mg/dl) and apolipoprotein B (+11 mg/dl) as well as lower mean levels of high density lipoprotein (HDL) cholesterol (-15 mg/dl) and apolipoprotein A-I (-19 mg/dl). Additionally, men were more overweight, consumed more alcohol, and exercised more frequently than women but were less likely to smoke cigarettes. Controlling for these characteristics, however, did not alter the differences in lipoprotein levels between men and women. In contrast, adjustment for WHR (which was greater among men) reduced the sex differences in levels of apolipoprotein B (by 98%), triglycerides (by 94%), HDL cholesterol (by 33%), and apolipoprotein A-I (by 21%). Similar results were obtained using analysis of covariance, stratification, or matching; at comparable levels of WHR, differences in lipid and lipoprotein levels between men and women were greatly reduced. Although these results are based on cross-sectional analyses of employed adults and need to be replicated in other populations, the findings emphasize the relative importance of body fat distribution. Whereas generalized obesity and body fat distribution are associated with lipid levels, fat distribution (or a characteristic influencing fat patterning) can be an important determinant of sex differences in levels of triglycerides, HDL cholesterol, and apolipoproteins B and A-I.
Outcome after a "perfect" Fontan operation.
Authors: Fontan F , Kirklin J W , Fernandez G , Costa F , Naftel D C , Tritto F , Blackstone E H
Published: June 2011

A study was undertaken to determine the early and long-term outcomes dictated by the Fontan state per se (a state in which the force driving pulmonary blood flow is solely or largely a residue, in the systemic venous pressure, of the main ventricular chamber's contractile force) and the transition (by surgery) to it from the state of congenital heart disease under optimal conditions (after a "perfect" Fontan operation). The primary study design used a solution of a multivariate risk factor equation for death, by which survival rate under optimal conditions was predicted to be 92%, 89%, 88%, 86%, 81%, and 73% at 1 month, 6 months, and 1, 5, 10, and 15 years, respectively, after the Fontan operation. The hazard function (instantaneous risk of death at each moment in time after the operation) had an early rapidly declining phase of hazard that at about 6 months began to give way to a late hazard phase, which was rising by about 6 years after surgery. A secondary study design, using the theory of competing risks, yielded survival and hazard function information very similar to that of the primary study design. The functional capacity of the patients as expressed by New York Heart Association class was less, the longer the period of follow-up. No risk factors (other than older age at time of surgery) were found for the late decline in survival or the decline in functional status. The inference is that the premature decline in survival and functional status and the late rise in hazard function are from the Fontan state per se and that the Fontan operation is, therefore, palliative but not curative.
Ventricular volume characteristics in double-inlet left ventricle before and after septation.
Authors: Nakazawa M , Aotsuka H , Imai Y , Kurosawa H , Fukuchi S , Satomi G , Takao A
Published: June 2011

Septation is one of the surgical choices for double-inlet left ventricle, yet postoperative hemodynamics have not been well defined. We studied ventricular volume characteristics in 10 patients with double-inlet left ventricle before and after septation. Preoperative end-diastolic volume (EDV) of the ventricle was 291 +/- 111% (+/- SD) of normal and ejection fraction (EF) was 0.59 +/- 0.07. Postoperatively, EDV of the right-sided ventricle (RV) was 82 +/- 24%, and EDV of the left-sided ventricle (LV) was 153 +/- 41%. Ejection fraction of the RV was 0.77 +/- 0.10, and LVEF was 0.49 +/- 0.13. On the short-axis view of two-dimensional echocardiography, fractional change of the cross-sectional area was 0.65 +/- 0.16 for the RV and 0.23 +/- 0.11 for the LV. Fractional shortening of the septum-to-ventricular free wall axis was 0.51 +/- 0.17 in the RV and -0.05 +/- 0.09 in the LV. Analysis of the curvature of the new septum during cardiac cycle on two-dimensional echocardiography revealed that the septum shifted to the right side during systole in all patients in whom the systolic LV/RV pressure ratio was larger than 1.0. The septum shifted toward the LV during diastole in eight patients in whom end-diastolic pressure in the RV was higher than or equal to that in the LV, whereas it remained in the right side in two patients with higher left-side pressure. The cardiac index of these two patients was 2.4 and 2.6 l/min/m2, respectively, whereas it averaged 4.4 +/- 1.0 l/min/m2 in the other eight patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Endothelium-dependent vascular relaxation is abnormal in the coronary microcirculation of atherosclerotic primates.
Authors: Sellke F W , Armstrong M L , Harrison D G
Published: June 2011

Atherosclerosis impairs endothelium-dependent relaxation of large conduit arteries. Because coronary resistance vessels are spared from the development of overt atherosclerosis, endothelium-dependent responses were examined in these vascular segments. Malaysian cynomolgus monkeys (n = 6) were made atherosclerotic by being fed a 0.7% cholesterol diet for 18 months. Control monkeys (n = 6) were fed a standard diet. Coronary microvessels (122-220 microns) were studied in a pressurized (20 mm Hg), no-flow state using a video-imaging apparatus. Relaxations of microvessels, preconstricted with the thromboxane analogue U46619, were determined in response to acetylcholine, bradykinin, the calcium ionophore A23187, adenosine, and sodium nitroprusside. Microvascular relaxations to bradykinin and A23187 were reduced in atherosclerotic monkeys compared with controls, whereas acetylcholine produced additional contraction in atherosclerotic monkeys. Responses of preconstricted microvessels to adenosine and sodium nitroprusside were identical in atherosclerotic and control animals. Indomethacin did not alter responses in control or atherosclerotic animals. Histologic examination revealed neither intimal thickening nor plaque formation in microvessels of this size class despite marked changes in conduit arteries. Electron microscopy showed minor alterations of endothelial cell morphology in microvessels of atherosclerotic animals. In conclusion, long-term hypercholesterolemia markedly impairs endothelium-dependent vascular relaxation in the coronary microcirculation where overt atherosclerosis does not develop. These changes in endothelial cell function may significantly alter regulation of myocardial perfusion by neurohumoral stimuli.
Positron emission tomographic imaging of cardiac sympathetic innervation and function.
Authors: Goldstein D S , Chang P C , Eisenhofer G , Miletich R , Finn R , Bacher J , Kirk K L , Bacharach S , Kopin I J
Published: June 2011

Sites of uptake, storage, and metabolism of [18F]fluorodopamine and excretion of [18F]fluorodopamine and its metabolites were visualized using positron emission tomographic (PET) scanning after intravenous injection of the tracer into anesthetized dogs. Radioactivity was concentrated in the renal pelvis, heart, liver, spleen, salivary glands, and gall bladder. Uptake of 18F by the heart resulted in striking delineation of the left ventricular myocardium. Pretreatment with desipramine markedly decreased cardiac positron emission, consistent with dependence of the heart on neuronal uptake (uptake-1) for removal of circulating catecholamines. In reserpinized animals, cardiac positron emission was absent within 30 minutes after injection of [18F]-6-fluorodopamine, demonstrating that the emission in untreated animals was from radioactive labeling of the sympathetic storage vesicles. Decreased positron emission from denervated salivary glands confirmed that the tracer was concentrated in sympathetic neurons. Radioactivity in the gall bladder and urinary system depicted the hepatic and renal excretion of the tracer and its metabolites. Administration of tyramine or nitroprusside increased and ganglionic blockade with trimethaphan decreased the rate of loss of myocardial radioactivity. The results show that PET scanning after administration of [18F]fluorodopamine can be used to visualize sites of sympathetic innervation, follow the metabolism and renal and hepatic excretion of catecholamines, and examine cardiac sympathetic function.
Treatment of 150 cases of life-threatening digitalis intoxication with digoxin-specific Fab antibody fragments. Final report of a multicenter study.
Authors: Antman E M , Wenger T L , Butler V P , Haber E , Smith T W
Published: June 2011

One hundred fifty patients with potentially life-threatening digitalis toxicity were treated with digoxin-specific antibody fragments (Fab) purified from immunoglobulin G produced in sheep. The dose of Fab fragments was equal to the amount of digoxin or digitoxin in the patient's body as estimated from medical histories or determinations of serum digoxin or digitoxin concentrations. The youngest patient received Fab fragments within several hours of birth, and the oldest patient was 94 years old. Seventy-five patients (50%) were receiving long-term digitalis therapy, 15 (10%) had taken a large overdose of digitalis accidentally, and 59 (39%) had ingested an overdose of digitalis with suicidal intent. The clinical response to Fab was unspecified in two cases, leaving 148 patients who could be evaluated. One hundred nineteen patients (80%) had resolution of all signs and symptoms of digitalis toxicity, 14 (10%) improved, and 15 (10%) showed no response. After termination of the Fab infusion, the median time to initial response was 19 minutes, and 75% of the patients had some evidence of a response by 60 minutes. There were only 14 patients with adverse events considered to possibly or probably have been caused by Fab; the most common events were rapid development of hypokalemia and exacerbation of congestive heart failure. No allergic reactions were identified in response to Fab treatment. Of patients who experienced cardiac arrest as a manifestation of digitalis toxicity, 54% survived hospitalization.(ABSTRACT TRUNCATED AT 250 WORDS)
Two-dimensional echocardiography and Doppler color flow mapping in the diagnosis and prognosis of ventricular septal rupture.
Authors: Helmcke F , Mahan E F , Nanda N C , Jain S P , Soto B , Kirklin J K , Pacifico A D
Published: June 2011

Doppler color flow mapping in conjunction with two-dimensional echocardiography was used to evaluate ventricular septal rupture after myocardial infarction (seven anterior and eight inferior) in 15 patients and to correlate these findings with cardiac catheterization and surgical or autopsy data. Ventricular septal rupture was diagnosed by turbulent flow traversing the ventricular septum. The direction and velocity of shunt flow was determined by color M-mode and conventional Doppler methods. In all patients, Doppler color flow mapping correctly defined the site of septal rupture, which occurred at areas of discordant septal wall motion or "hinge points" (six posterior inlet, three anterior inlet, and six apical trabecular septum). Each of three patients with moderate tricuspid regurgitation and three of four patients with right-to-left shunting during diastole died, and all had an elevated right ventricular end-diastolic pressure. Right ventricular wall motion index was significantly higher in the patients who died compared with those who survived (mean +/- SEM; 2.8 +/- 0.2 vs. 2.0 +/- 0.2, p = 0.012), but there was no difference in left ventricular wall motion index. The rupture size measured by Doppler color flow imaging (1.7 +/- 0.1 cm) correlated with the size determined during surgery or autopsy (1.8 +/- 0.2 cm, r = 0.68, p = 0.022) and the pulmonic-to-systemic shunt flow ratio by cardiac catheterization (2.4:1 +/- 0.3, r = 0.74, p = 0.004). Color-guided continuous-wave Doppler estimates of right ventricular systolic pressure (47 +/- 2 mm Hg) correlated with cardiac catheterization measurements (48 +/- 3 mm Hg, r = 0.90, p = 0.0002).(ABSTRACT TRUNCATED AT 250 WORDS)
Prostaglandin I2 half-life regulated by high density lipoprotein is decreased in acute myocardial infarction and unstable angina pectoris.
Authors: Aoyama T , Yui Y , Morishita H , Kawai C
Published: June 2011

To investigate the prostaglandin I2 (PGI2) half-life regulated by high density lipoprotein (HDL) in patients with coronary artery disease (CAD), we determined the stability of PGI2 and serum apolipoprotein A-I (Apo A-I) and apolipoprotein A-II (Apo A-II) levels in four age-matched groups of patients: controls (n = 17), angina pectoris (n = 18), unstable angina pectoris (n = 17), myocardial infarction (n = 19) (acute phase, 3.6 +/- 1.7 hours from onset; subacute phase, 75 +/- 15 hours from onset in the same patients). Serum PGI2 half-life and total serum Apo A-I levels were lower in the CAD group than in the control group. PGI2 was least stable in patients with unstable angina and the acute phase of myocardial infarction. In these patients, the molar ratio of Apo A-I to Apo A-II and HDL-associated Apo A-I levels were decreased, and free Apo A-I levels were increased. After in vitro incubation of HDL with increasing amounts of Apo A-II, Apo A-I in HDL was displaced by Apo A-II, with the parallel decrease in stability of PGI2. Free Apo A-I cannot stabilize PGI2. HDL-associated Apo A-I, whose amount is affected by Apo A-II, stabilized PGI2 and correlated well with stability of PGI2 in patients with CAD and control patients. Decreased PGI2 half-life may play an important role in the pathogenesis of atherosclerosis and thrombus formation in the coronary arteries, especially thrombus formation during an acute coronary event.
Hemodynamic mechanisms of antianginal action of calcium channel blocker nisoldipine in dynamic exercise-induced angina.
Authors: Yokota M , Miyahara T , Iwase M , Watanabe M , Matsunami T , Kamihara S , Koide M , Saito H , Takeuchi J
Published: June 2011

To investigate the mechanism of antianginal action of the calcium channel blocker nisoldipine and to determine the reproducibility of the clinical and hemodynamic events induced by supine leg exercise, 30 patients with stable effort angina pectoris were studied. They were divided into two groups; one group of 19 patients received a single 10-mg dose of nisoldipine orally, and the other group of 11 patients received a single dose of placebo orally. Chest pain was induced in all of 30 patients during the control exercise test. After nisoldipine administration, chest pain was not induced in 13 of 19 patients and was of lessened severity in five patients with the same work load as those performing control exercise. ST segment at peak exercise showed less severe depression after nisoldipine. Systemic vascular resistance was reduced by 38% (p less than 0.001) at rest and 22% (p less than 0.001) at peak exercise, and coronary vascular resistance was reduced by 31% (p less than 0.01) at rest and 18% (p less than 0.01) at peak exercise. Pulmonary artery wedge pressure fell from 6 +/- 1 to 3 +/- 1 mm Hg (p less than 0.001) at rest and from 28 +/- 3 to 11 +/- 2 mm Hg (p less than 0.001) at peak exercise. Coronary sinus flow at rest and myocardial oxygen uptake both at rest and during exercise was not modified by nisoldipine. However, coronary sinus flow at peak exercise increased significantly from 219 +/- 24 to 249 +/- 31 ml/min (p less than 0.01) after nisoldipine, and myocardial oxygen uptake was not significantly changed despite decreased coronary vascular resistance. The clinical and hemodynamic events induced by the exercise during invasive studies (except pulmonary artery wedge pressure at rest) were reproducible after placebo administration. Our data demonstrate that increased coronary blood flow could be the major mechanism of the antianginal action of nisoldipine in supine leg exercise-induced angina.
Physiological and immunopathological consequences of active immunization of spontaneously hypertensive and normotensive rats against murine renin.
Authors: Michel J B , Sayah S , Guettier C , Nussberger J , Philippe M , Gonzalez M F , Carelli C , Galen F X , Menard J , Corvol P
Published: June 2011

Spontaneously hypertensive Okamoto-strain rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were actively immunized with mouse renin to investigate the effect on blood pressure of blocking the renin-angiotensinogen reaction. Ten male SHR and 10 male WKY rats were immunized with purified mouse submandibular gland renin. Control rats were immunized with bovine serum albumin. Antirenin antibodies were produced by both SHR and WKY rats, but renin-immunized SHR had higher titers of circulating renin antibodies after three injections. The increase in renin antibody in renin-immunized SHR was associated with a significant drop in blood pressure (tail-cuff method) that became similar to that of the WKY control rats after four injections. The blockade by antirenin immunoglobulins of the renin-angiotensinogen reaction also decreased the blood pressure of normotensive rats. Perfusion of renin-immunized rats with mouse submandibular renin (10 micrograms) in vivo caused no increase in blood pressure. Perfusion of renin-immunized, salt-depleted SHR with converting enzyme inhibitor caused no further decrease in blood pressure but significantly decreased blood pressure in salt-depleted control rats. The presence of circulating renin antibodies was associated with low plasma renin activity (0.31 +/- 0.23 ng angiotensin I [Ang I]/ml/hr). Plasma renin activity was unchanged in control animals (13.1 +/- 3.9 ng Ang I/ml/hr in control SHR, 13.9 +/- 3.2 ng Ang I/ml/hr in control WKY rats). Renin antibody-rich serum produced a dose-dependent inhibition of rat renin enzymatic activity in vitro. The chronic blockade of the renin-angiotensinogen reaction in renin-immunized SHR produced an almost-complete disappearance of Ang II (0.8 %/- 7 fmol/ml; control SHR, 30.6 +/- 15.7 fmol/ml) and a 50% reduction in urinary aldosterone. Renin immunization was never associated with a detectable loss of sodium after either 10 or 24 weeks. The glomerular filtration rate was not decreased 10 weeks after renin immunization, whereas blood pressure was significantly decreased, plasma renin activity was blocked, and renal plasma flow was increased. The ratio of left ventricular weight to body weight after 24 weeks was significantly below control levels in renin-immunized WKY rats and SHR. Histological examination of the kidney of renin-immunized SHR showed a chronic autoimmune interstitial nephritis characterized by the presence of immunoglobulins, mononuclear cell infiltration, and fibrosis around the juxtaglomerular apparatus. These experiments demonstrate that chronic specific blockade of renin decreases blood pressure in a genetic model of hypertension in which the renin-angiotensin system is not directly involved.(ABSTRACT TRUNCATED AT 400 WORDS)
Endothelial modulation of the coronary vasculature in vessels perfused via mature collaterals.
Authors: Sellke F W , Quillen J E , Brooks L A , Harrison D G
Published: June 2011

Previous in vivo studies have shown that vasopressin, which releases the endothelium-derived relaxing factor and constricts coronary smooth muscle, produces augmented constriction of coronary microvessels perfused by mature collaterals. We hypothesized that chronic perfusion through collaterals produces endothelial dysfunction in the recipient vasculature. Mature collaterals were stimulated in mongrel dogs by the ameroid constrictor technique. After 3-6 months, rings of conduit vessels (obtuse marginals) were studied in organ chambers, and coronary microvessels (100-220 microns) were studied in a pressurized, no-flow state with a microvessel imaging apparatus. Eleven dogs were used as controls. Large vessels were preconstricted with prostaglandin F2 alpha to 30-70% of the maximum potassium chloride tension, and microvessels were preconstricted to 20-60% of the baseline diameter with the thromboxane mimetic U46619. Relaxations to the receptor-mediated agents acetylcholine and ADP were markedly impaired in collateral-dependent coronary microvessels, whereas relaxations to nitroglycerin were enhanced compared with microvessels from control dogs. Relaxation to the calcium ionophore A23187, which releases the endothelium-derived relaxing factor through nonreceptor-mediated mechanisms, were similar in control and ameroid microvessels. Constriction to vasopressin was augmented in collateral-dependent microvessels compared with controls. Responses to all agonists were similar between control and collateral-dependent large vascular rings. In conclusion, chronic perfusion through collateral vessels selectively impairs receptor-mediated endothelium-dependent relaxations and augments constriction to vasopressin in the coronary microcirculation. These findings may have important implications regarding neurohumoral regulation of perfusion to collateral-dependent myocardium.
Salt and water retention and calcium blockade in uremia.
Authors: London G M , Marchais S J , Guerin A P , Metivier F , Safar M E , Fabiani F , Froment L
Published: June 2011

Blood pressure, echocardiography, and aortic and peripheral arterial pulse-wave velocity were studied in 40 hypertensive patients on long-term hemodialysis during a 24-week administration of nitrendipine (1,4-dihydro-2,6-dimethyl-4-[m-nitrophenyl]-3,5-pyridine-dicarboxylic acid ethyl methylester) monotherapy. In a double-blind placebo-randomized study, nitredipine effectively lowered the blood pressure (p less than 0.001) before hemodialysis without causing postdialysis hypotension. The antihypertensive effect of nitrendipine was greater in patients with significant salt and water retention, as indicated by interdialytic body weight gain (delta BW), that is, a significant correlation was observed between delta BW and the decrease in blood pressure (r = 0.72; p less than 0.001). The antihypertensive effect was not related to age, pretreatment plasma renin activity, or serum-ionized calcium concentration. After nitrendipine, a time-related decrease in aortic (p less than 0.005) and femoral (p less than 0.05) pulse-wave velocity was observed with a significant time-treatment interaction (p less than 0.01). Nitrendipine treatment did not influence left ventricular mass (which was positively correlated with delta BW; p less than 0.01) but was associated with an increase in the left ventricular ejection fraction. The increase in ejection fraction was correlated with changes in aortic pulse-wave velocity (r = 0.548; p less than 0.02) but not with changes in blood pressure (r = 0.352; p = 0.19) or delta BW.(ABSTRACT TRUNCATED AT 250 WORDS)
Left ventricular volume measurement using cardiac axis nuclear magnetic resonance imaging. Validation by calibrated ventricular angiography.
Authors: Cranney G B , Lotan C S , Dean L , Baxley W , Bouchard A , Pohost G M
Published: June 2011

Proton nuclear magnetic resonance (NMR) imaging has the potential to serially assess left ventricular (LV) volumes with optimal accuracy because it is a high-resolution, three-dimensional, noninvasive modality. Previous NMR studies to assess LV volumes have been suboptimal, as they have used either planes aligned with the axes of the body, which are compromised by partial volume effects, or spin-echo techniques that have been time-consuming to acquire and analyze. Accordingly, for LV volume measurement, we developed a gradient-echo (cine) NMR strategy that uses two orthogonal planes intersecting along the intrinsic long axis of the heart (two-chamber and four-chamber). This approach was validated against calibrated contrast biplane LV cineangiography (CATH) and also compared with a previously reported short-axis spin-echo NMR method. Twenty-one patients underwent CATH and NMR (long-axis, n = 21; short-axis, n = 14) within a 3-day interval. Although both long- and short-axis NMR LV volumes and ejection fractions correlated well with CATH (r greater than 0.90, p less than 0.001 in all), end-diastolic volumes by both long-axis (161 +/- 85 ml) and short-axis (151 +/- 81 ml) NMR were systematically less than those by CATH (182 +/- 85 ml) (p less than 0.05). Consequently, ejection fractions by long-axis (48 +/- 17%) and short-axis (49 +/- 17%) NMR consistently underestimated those by CATH (54 +/- 16%, p less than 0.05). End-systolic volumes by long-axis (94 +/- 71 ml) and short-axis (87 +/- 72 ml) NMR were not significantly different from those by CATH (92 +/- 69 ml). Both NMR techniques had low intraobserver and interobserver variation (less than 11%); however, short-axis spin-echo NMR involved longer acquisition/reconstruction (35 versus 18 minutes) and analysis (25 versus 10 minutes) times. We conclude that both short-axis spin-echo and long-axis gradient-echo NMR approaches reliably estimate LV volumes. Currently, the long-axis strategy appears more practical for clinical use because the scan and analysis times are relatively short.
Inhibition of platelet adhesion to surfaces of extracorporeal circuits by disintegrins. RGD-containing peptides from viper venoms.
Authors: Musial J , Niewiarowski S , Rucinski B , Stewart G J , Cook J J , Williams J A , Edmunds L H
Published: June 2011

Previous studies indicate that exposure of fibrinogen receptors associated with glycoprotein IIb/IIIa complex contributes to platelet loss during cardiopulmonary bypass. Recently, we isolated a number of RGD (Arg-Gly-Asp)-containing, low molecular weight, cysteine-rich peptides from viper venoms. These peptides, which we propose to call "disintegrins," block platelet-fibrinogen interaction and platelet aggregation. We compared the effect of RGDS (Arg-Gly-Asp-Ser) and four disintegrins (echistatin, flavoridin, albolabrin, and bitistatin) on platelet behavior in a membrane oxygenator. During simulated extracorporeal circulation for 2 hours, platelet count decreased to about 30% of initial values. Addition of echistatin (60-200 nM), albolabrin (60-200 nM), bitistatin (60 nM), and flavoridin (45 nM) significantly inhibited platelet loss in the circuit. RGDS (33 microM) did not show any significant inhibitory effect. ADP-induced platelet aggregation was inhibited in samples of platelet-rich plasma taken from the circuits containing disintegrins. However, echistatin appeared to be a more potent inhibitor of platelet aggregation, whereas albolabrin and flavoridin interfered more selectively with platelet loss from the circuit. Echistatin prevented the accumulation of glycoprotein IIIa on the surface of the circuit. Echistatin (60-200 nM), flavoridin (45 nM), bitistatin (60 nM), and albolabrin (200 nM) significantly inhibited the loss of beta-thromboglobulin from platelets into circulating plasma. Electron microscopy studies demonstrated shape change but not degranulation in platelets circulating in the presence of 200 nM echistatin. On the other hand, this peptide (up to 1,000 nM) did not prevent loss of alpha granules and beta-thromboglobulin from thrombin-stimulated platelets, although it prevented their aggregation. In conclusion, disintegrins protect platelets in the circuit by preventing their adhesion to surfaces and, therefore, preventing fragmentation of adhered platelets under the shear stress of flowing blood. This study indicates that disintegrins may be potential candidates for platelet protection during cardiopulmonary bypass.
Insulin-dependent diabetes mellitus mortality. The risk of cigarette smoking.
Authors: Moy C S , LaPorte R E , Dorman J S , Songer T J , Orchard T J , Kuller L H , Becker D J , Drash A L
Published: June 2011

The relation between cigarette smoking and mortality was examined prospectively in a population of adult insulin-dependent diabetes mellitus (IDDM) patients. In 1981, information on smoking history and other health and lifestyle factors was obtained by questionnaire from 93% of the 723 patients included in the Children's Hospital of Pittsburgh IDDM registry who were diagnosed between 1950 and 1964. Vital status as of January 1, 1988 was ascertained for 98% of the 548 patients who participated in the baseline survey and were alive as of January 1, 1982. Fifty-four cases died during the 6-year follow-up (32 male, 22 female). Proportional hazards analysis revealed that heavy smoking was a significant independent predictor of all-cause mortality among females but not males. The excess mortality in female diabetics was explained primarily by a marked excess risk of coronary heart disease mortality in smokers. These data strongly suggest that cigarette smoking, especially among diabetic females, should be avoided in order to improve longevity.
Clinical features of amiodarone-induced pulmonary toxicity.
Authors: Dusman R E , Stanton M S , Miles W M , Klein L S , Zipes D P , Fineberg N S , Heger J J
Published: June 2011

The incidence and clinical predictors of amiodarone pulmonary toxicity were examined in 573 patients treated with amiodarone for recurrent ventricular (456 patients) or supraventricular (117 patients) tachyarrhythmias. Amiodarone pulmonary toxicity was diagnosed in 33 of the 573 patients (5.8%), based on symptoms and new chest radiographic abnormalities (32 of 33 patients) and supported by abnormal pulmonary biopsy (13 of 14 patients), low pulmonary diffusion capacity (DLCO) (nine of 13 patients), and/or abnormal gallium lung scan (11 of 16 patients). Toxicity occurred between 6 days and 60 months of treatment for a cumulative risk of 9.1%, with the highest incidence occurring during the first 12 months (18 of 33 patients). Older patients developed it more frequently (62.7 +/- 1.7 versus 57.4 +/- 0.5 years, p = 0.018), with no cases diagnosed in patients who started therapy at less than 40 years of age. Gender, underlying heart disease, arrhythmia, and pretreatment chest radiographic, spirometric, or lung volume abnormalities did not predict development of amiodarone pulmonary toxicity, whereas pretreatment DLCO was lower in the group developing it (76.0 +/- 5.5% versus 90.4 +/- 1.4%, p = 0.01). There was a higher mean daily amiodarone maintenance dose in the pulmonary toxicity group (517 +/- 25 versus 409 +/- 6 mg, p less than 0.001) but no difference in loading dose. No patient receiving a mean daily maintenance dose less than 305 mg developed pulmonary toxicity. Patients who developed toxicity had higher plasma desethylamiodarone (2.34 +/- 0.18 versus 1.92 +/- 0.04 micrograms/ml, p = 0.009) but not amiodarone concentrations during maintenance therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Coronary atherectomy. Clinical, angiographic, and histological findings and observations regarding potential mechanisms.
Authors: Safian R D , Gelbfish J S , Erny R E , Schnitt S J , Schmidt D A , Baim D S
Published: June 2011

Between August 5, 1988 and August 1, 1989, we attempted percutaneous directional coronary atherectomy of 76 lesions, including 42 primary lesions and 34 restenosis lesions that developed after one or more prior interventions. The procedure was successful in 67 lesions (88%), with a decrease in diameter stenosis from 80 +/- 11% to 5 +/- 15% after atherectomy (p less than 0.01). One or more complications occurred in six patients (9%), including non-Q wave myocardial infarction (three patients, 4.5%), femoral arterial injury requiring surgical repair (two patients, 3%), and proximal dissection leading to emergency bypass surgery (one patient, 1.5%). Despite these favorable acute results, the 6-month lesion restenosis rate was 30% by life-table analysis. Light microscopy of retrieved tissue revealed atherosclerotic plaque in 94%, media in 67%, and adventitia in 27%. Intimal proliferation was present in 97% of the restenosis lesions but was also evident in 33% of primary lesions. Tissue weight from 27 lesions averaged 18.5 mg (range, 5.8-45.1 mg), which is not adequate to explain the entire angiographic improvement. Thus, part of the improvement in lumen diameter appears to be due to mechanical dilatation rather than to tissue removal alone. Atherectomy can predictably treat selected coronary lesions with overall safety comparable to that of conventional balloon angioplasty, although the procedure as currently performed does not derive all of its benefit from tissue removal and does not appear to prevent restenosis.
Automated quantitation of indexes of coronary lesion complexity. Comparison between patients with stable and unstable angina.
Authors: Kalbfleisch S J , McGillem M J , Simon S B , DeBoe S F , Pinto I M , Mancini G B
Published: June 2011

Analysis of lesion morphology is becoming increasingly important in the study of coronary artery disease. Lesion irregularity has been shown to be one of the most important predictive features for development of myocardial infarction. Most studies to date have used only qualitative assessments of morphology and are thus subject to variability and lack of standardization inherent in subjective visual inspection. We describe a new approach that allows quantitation of lesion morphology. Fifty-nine patients with unstable angina and 17 patients with stable angina were compared. Five morphometric parameters were tested (peaks per centimeter, summed maximum error per centimeter, integrated error per centimeter, number of major features per centimeter, and scaled edge length ratio), four of which were significantly different between the two groups and indicated greater lesion complexity in unstable compared with stable angina patients. No correlation was found between the parameters tested and the degree of luminal narrowing, showing the method's independence from traditional assessments of lesion severity. Excellent intraobserver and interobserver reproducibility was found for all of the parameters. This technique provides a more rigorous approach for analysis of lesion morphology than has previously been available, may provide a method for premorbid detection of high-risk lesions amenable to interventional therapy, and is especially well suited to detect subtle changes in lesion morphology after therapeutic interventions because the parameters are derived on a continuous scale and are not categorical.
Natural history of left ventricular size and function after acute myocardial infarction. Assessment and prediction by echocardiographic endocardial surface mapping.
Authors: Picard M H , Wilkins G T , Ray P A , Weyman A E
Published: June 2011

To investigate the natural history of regional dyssynergy and left ventricular size after myocardial infarction, 57 patients with a first Q wave myocardial infarction (18 anterior, 35 inferior, and four apical by echocardiography) were studied by two-dimensional echocardiography and compared with 30 control patients. Measurements from the echocardiograms were used to construct maps of the left ventricular endocardial surface from which the endocardial surface area index (ESAi) and the percent of the endocardial surface area involved by abnormal wall motion (%AWM) were calculated. The maps from entry and 3-month echocardiograms were used to classify patients based on changes in ESAi and abnormal wall motion. Two subgroups of patients were identified at entry--those with a normal ESAi (group 1, n = 50) and those with an increased ESAi (group 2, n = 7). Group 1 patients was subdivided at 3 months by changes occurring in ESAi (1A, 5% increase [n = 19]; 1B, no change [n = 23]; 1C, 5% decrease [n = 8]). The increase in ESAi (64.9 +/- 5.2 to 75.4 +/- 7.5 cm2/m2, p less than 0.0001) in group 1A was associated with global ventricular dilatation (n = 11) and clinically silent infarct extension (n = 8). Groups 1B and 1C were composed predominantly of patients with inferior infarctions, and all exhibited either no change or a significant decrease in infarct size (infarct regression). Group 2 patients demonstrated a continued increase in ESAi by 3 months (88.2 +/- 10.0 to 101.4 +/- 15.5 cm2/m2, p less than 0.007). This group comprised only patients with anterior infarctions, and all exhibited infarct expansion at the left ventricular apex. The changes in left ventricular size and functional infarct size are heterogeneous after acute myocardial infarction and relate to the initial endocardial surface area, infarct location, and functional infarct size.
Long QT syndrome. New electrocardiographic characteristics.
Authors: Benhorin J , Merri M , Alberti M , Locati E , Moss A J , Hall W J , Cui L
Published: June 2011

The long QT syndrome is electrocardiographically characterized by a prolonged QT interval and by several other, more subtle, ST-T-U wave abnormalities, most of which have not been quantified. To determine the possible usefulness of several new electrocardiographic characteristics in identifying patients with known long QT syndrome, logistic regression models were applied to a data base of seven new, relatively independent, electrocardiographic repolarization variables. These were measured on digitized 12-lead electrocardiograms of 315 normal subjects and 37 patients with the long QT syndrome (members of well-identified long QT syndrome families, QTc greater than 0.44 second, 27% symptomatic), who ranged in age from 17 to 60 years. Electrocardiographic variables that independently differentiated (p less than 0.001) patients with long QT syndrome from normal subjects included quantitative measures of repolarization: early duration, rate, T wave symmetry, late phenomena, and heterogeneity. All selected repolarization variables except the early duration variable were essentially independent of the QTc (r2 less than 0.15), and all contributed significantly to the identification of patients with long QT syndrome. A classification model of five electrocardiographic predictor variables resulted in an estimated sensitivity (95% confidence interval) of 92.6% (81.6-100%) and an estimated specificity (95% confidence interval) of 95.8% (93.6-98.1%). This model performed significantly better than an alternative classification model that was based on the early duration variable as a single predictor variable. The symptomatic status of patients with long QT syndrome could not be predicted by any combination of the electrocardiographic variables in the investigated model.