bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of age on endothelium-dependent vasodilation of resistance coronary artery by acetylcholine in humans.
Authors: Egashira K , Inou T , Hirooka Y , Kai H , Sugimachi M , Suzuki S , Kuga T , Urabe Y , Takeshita A
Published: June 2012

BACKGROUND

It has been suggested that endothelium-related vasomotion is important in the control of coronary circulation. Our goal was to determine if endothelium-dependent dilation of the coronary vasculature was altered with aging in 18 patients with atypical chest pain (age, 23-70 years) who had angiographically normal coronary arteries and no coronary risk factors.

METHODS AND RESULTS

We infused an endothelium-dependent vasodilator acetylcholine (1, 3, 10, and 30 micrograms/min) and an endothelium-independent vasodilator papaverine (10 mg) into the left coronary artery. The large coronary diameter was assessed by arteriography, and the increase in coronary blood flow was measured using the intracoronary Doppler catheter technique. Acetylcholine increased coronary blood flow in a dose-dependent manner with no changes in arterial pressure and heart rate. The maximum increase in coronary blood flow evoked by acetylcholine varied widely among patients (increase in coronary blood flow ranged from 200% to 560%) and was correlated significantly with aging (r = -.86, P < .001), whereas the peak coronary blood flow response to papaverine was affected slightly by aging (r = -.44, P = .07). The percent increase in blood flow response to acetylcholine to the response to papaverine correlated with aging (r = -.87, P < .001). The slope of the coronary blood flow response to acetylcholine also correlated significantly with aging. The large epicardial coronary artery response to the low doses of acetylcholine (< or = 10 micrograms/min) correlated inversely with aging.

CONCLUSIONS

The results of this study suggest that endothelium-dependent dilation of coronary arteries evoked by acetylcholine may be decreased with aging in humans.
Increased plasma levels of brain natriuretic peptide in patients with acute myocardial infarction.
Authors: Morita E , Yasue H , Yoshimura M , Ogawa H , Jougasaki M , Matsumura T , Mukoyama M , Nakao K
Published: June 2012

BACKGROUND

Brain natriuretic peptide is a novel natriuretic peptide that is secreted predominantly from the ventricles, and its plasma levels have been shown to be markedly increased in patients with chronic congestive heart failure. This study was designed to examine the plasma levels of brain natriuretic peptide as well as atrial natriuretic peptide in patients with acute myocardial infarction.

METHODS AND RESULTS

We examined the plasma levels of brain natriuretic peptide as well as atrial natriuretic peptide in 50 consecutive patients (36 men and 14 women; mean age, 66 years) with acute myocardial infarction over the time course of 4 weeks. The plasma level of brain natriuretic peptide was significantly increased on admission in patients with acute myocardial infarction compared with controls (92 +/- 28 versus 5.2 +/- 0.5 pg/mL, P < .01) and reached the peak level of 319 +/- 58 pg/mL at 16.4 +/- 0.7 hours after admission. Thereafter, the level decreased and then again increased, forming the second peak of 277 +/- 66 pg/mL on day 5. The level then decreased gradually but was still much higher in the fourth week than that of controls (149 +/- 47 versus 5.2 +/- 0.5 pg/mL, P < .001). On the other hand, the plasma atrial natriuretic peptide level already had been increased at the time of admission compared with controls (116 +/- 14 versus 39.5 +/- 2.6 pg/mL, P < .01) and decreased thereafter, again increasing and making a small peak on day 2 to 3. The time course of the plasma brain natriuretic peptide level could be divided into two patterns: a monophasic pattern with one peak at about 16 hours after admission and a biphasic pattern with two peaks at about 16 hours and 5 days after admission. There were significantly more patients with anterior infarction, congestive heart failure, higher level of maximal creatine kinase-MB isoenzyme, and lower left ventricular ejection fraction in the biphasic group than in the monophasic group.

CONCLUSIONS

We conclude that the plasma level of brain natriuretic peptide is increased markedly in patients with acute myocardial infarction and may reflect the degree of left ventricular dysfunction in these patients.
Molecular forms of atrial natriuretic factor in normal and failing human myocardium.
Authors: Rodeheffer R J , Naruse M , Atkinson J B , Naruse K , Burnett J C , Merrill W H , Frist W H , Demura H , Inagami T
Published: June 2012

BACKGROUND

Atrial natriuretic factor (ANF) is produced by myocardial tissue, and the plasma ANF concentration is known to be elevated in congestive heart failure (CHF). Data from animal models indicate that myocardial concentrations of ANF are depleted in CHF, and this has given rise to the hypothesis that CHF is characterized by depletion of stored ANF. To date, the molecular forms of ANF and their concentrations in atrial and ventricular myocardium remain poorly characterized in the normal and the failing human heart.

METHODS AND RESULTS

We measured ANF concentrations in fresh tissue from failing human hearts explanted at the time of cardiac transplantation and from organ donors whose normal hearts could not be used for transplantation. We determined total ANF and alpha, beta, and gamma ANF concentrations in the right and left atrial appendages, atrial free walls, and ventricles. In normal hearts, ANF concentration in the atrial appendages was 40-fold higher than ANF in the rest of the atrial free wall and in the ventricles. In the failing hearts, atrial appendage ANF concentrations increased 5- to 10-fold, and atrial free wall ANF concentrations increased 200-fold. Analysis of molecular forms of ANF demonstrated significant increases in the gamma and beta forms in the left atrial appendage of failing hearts. alpha, beta, and gamma ANF forms were also significantly increased in right and left atrial free wall tissue from failing hearts. In addition, failing hearts were characterized by absolute and relative increases in the precursor form gamma ANF.

CONCLUSIONS

These data from fresh tissues suggest that cardiac ANF stores are not decreased in severe CHF in humans; rather, chronic CHF is characterized by marked increases in atrial ANF tissue concentrations, particularly the beta and gamma ANF forms. These findings are consistent with intracellular accumulation of precursor ANF forms in severe chronic human CHF.
LDL subclass phenotypes and the insulin resistance syndrome in women.
Authors: Selby J V , Austin M A , Newman B , Zhang D , Quesenberry C P , Mayer E J , Krauss R M
Published: June 2012

BACKGROUND

Low-density lipoprotein (LDL) subclass phenotype B, characterized by predominance of small, dense LDL particles, is associated with elevated plasma triglycerides and apolipoprotein B and with lower high-density lipoprotein (HDL) cholesterol and apolipoprotein A-I. Because these abnormalities resemble the dyslipidemia of insulin resistance, we examined associations of LDL subclass phenotype with plasma insulin levels and with other aspects of the insulin resistance syndrome.

METHODS AND RESULTS

LDL subclass phenotypes were determined by gradient gel electrophoresis in 682 female twins aged 30 to 91 years who participated in the second examination of the Kaiser Permanente Women Twins Study. Prevalence of phenotype B and the intermediate phenotype (I) increased strongly with age, obesity, and non-insulin-dependent diabetes. In multivariate analysis of nondiabetic women, phenotype B or I was independently associated with each aspect of the insulin resistance syndrome, including higher plasma triglycerides, waist-hip ratio, fasting and postload insulin levels, and systolic blood pressure and lower HDL cholesterol levels after adjustment for age and body mass index. The prevalence of phenotype B or I rose progressively from 5.6% in women with no manifestations of the insulin resistance syndrome to 100% in women with four syndrome components. In 25 nondiabetic, monozygotic twin pairs discordant for subclass phenotype, the twins with phenotype B (or I) had significantly higher levels of body mass index, waist-hip ratio, and systolic blood pressure than their twins with phenotype A. Thus, nongenetic variation in these risk factors is important in explaining their associations with LDL subclass phenotype.

CONCLUSIONS

Small, dense LDL is an integral feature of the insulin resistance syndrome. Nongenetic (ie, behavioral or environmental) factors are important for the expression of the phenotype and for its association with other heart disease risk factors.
Suppression of insulin-induced sympathetic activation and vasodilation by dexamethasone in humans.
Authors: Scherrer U , Vollenweider P , Randin D , Jéquier E , Nicod P , Tappy L
Published: June 2012

BACKGROUND

Physiological hyperinsulinemia in lean human subjects stimulates sympathetic nerve activity and blood flow in skeletal muscle, but the underlying mechanism is unknown. Potential mechanisms include central neural or peripheral actions of insulin. Glucocorticoids may potentially interfere with both such actions and thereby may attenuate sympathoexcitatory and vasodilatory effects of insulin in skeletal muscle.

METHODS AND RESULTS

To determine whether insulin-induced sympathetic activation and vasodilation are attenuated by dexamethasone, we measured muscle sympathetic nerve activity and muscle blood flow during euglycemic hyperinsulinemia before and after short-term administration of this pharmacological agent. Insulin concentrations, which normally doubled sympathetic activity and markedly increased blood flow, had no such stimulatory effect after short-term dexamethasone administration. In contrast, responses to two noninsulin sympathetic stimuli, the Valsalva maneuver and immersion of the hand in ice water, and the vasodilatory response to calf vascular occlusion were not altered by dexamethasone.

CONCLUSIONS

These results demonstrate a dramatic impairment of insulin-induced sympathetic activation and vasodilation by dexamethasone in lean, healthy humans. This study suggests that dexamethasone administration to lean subjects may offer an experimental model to examine underlying mechanisms that regulate the interplay between cardiovascular, sympathetic, and metabolic effects of insulin.
Continuous 12-lead ST-segment recovery analysis in the TAMI 7 study. Performance of a noninvasive method for real-time detection of failed myocardial reperfusion.
Authors: Krucoff M W , Croll M A , Pope J E , Granger C B , O'Connor C M , Sigmon K N , Wagner B L , Ryan J A , Lee K L , Kereiakes D J
Published: June 2012

BACKGROUND

If a practical, reliable, noninvasive marker of failed reperfusion was available in real time, the benefits of further therapy in this patient subgroup could be tested. We developed a method of 12-lead ST-segment recovery analysis using continuously updated reference points to provide such a marker.

METHODS AND RESULTS

In this study, our method was prospectively tested in 144 patients given thrombolytic therapy early in myocardial infarction. All patients had 12-lead continuous ST-segment monitoring and acute angiography, each analyzed in an independent, blinded core laboratory. ST-segment recovery and re-elevation were analyzed up to the moment of angiography, at which time patency was predicted. Predictions were correlated to angiographic infarct artery flow, with TIMI flow 0 to 1 as occluded and TIMI flow 2 to 3 as patent. Infarct artery occlusion was seen on first injection in 27% of patients. The positive predictive value of incomplete ST recovery or ST re-elevation by our method was 71%, negative predictive value 87%, with 90% specificity and 64% sensitivity for coronary occlusion. ST recovery analysis predicted patency in 94% of patients with TIMI 3 flow versus 81% of patients with TIMI 2 flow and predicted occlusion in 57% of patients with collateralized occlusion versus 72% of patients with non-collateralized occlusion. In a regression model including other noninvasive clinical descriptors, ST recovery alone contained the vast majority of predictive information about patency.

CONCLUSIONS

In a blinded, prospective, angiographically correlated study design, 12-lead continuous ST-segment recovery analysis shows promise as a practical noninvasive marker of failed reperfusion that may contribute substantially to currently available bedside assessment. Our data also suggest that patients with TIMI 2 flow or with collateralized occlusions may represent a physiological spectrum definable with ST-segment recovery analysis.
Comparison of native prothrombin antigen with the prothrombin time for monitoring oral anticoagulant prophylaxis.
Authors: Kornberg A , Francis C W , Pellegrini V D , Gabriel K R , Marder V J
Published: June 2012

BACKGROUND

Oral anticoagulation is most frequently monitored using the prothrombin time, but an alternative approach is measurement of native, fully carboxylated, prothrombin antigen (NPA). We have correlated results of the prothrombin time and NPA with development of venous thrombosis or bleeding complications in a clinical trial of warfarin prophylaxis following total hip arthroplasty to determine the potential value of NPA measurement for monitoring oral anticoagulation.

METHODS AND RESULTS

Patients in one arm of a prospective, randomized trial received warfarin prophylactically beginning 10 to 14 days before total hip arthroplasty in a dose adjusted to prolong the international normalized ratio (INR) to 1.5 on the day of surgery and 2.5 after surgery. NPA was measured by ELISA, and the prothrombin time was measured using rabbit brain thromboplastin. Samples were tested from 97 patients, and data from 81 patients who had adequate venography were analyzed to correlate test results with occurrence of thrombosis. The prothrombin time and INR were less sensitive than NPA to the lowest intensities of anticoagulation, with the prothrombin time index increasing from 1.0 to 1.3 and the INR increasing from 1.0 to 2.0, whereas the NPA concentration decreased fourfold, from 200 to 50 micrograms/mL. There was little correlation between either the prothrombin time index or the INR and the development of thrombosis, whereas NPA concentrations were significantly higher on the day of surgery and on postoperative days 1, 3, 5, and 7 in patients who developed venous thrombosis. Higher concentrations of NPA were associated with an increased risk of venous thrombosis, but there was no relation between thrombosis and the prothrombin time index or INR. There was no significant correlation between surgical blood loss and prothrombin time index, INR, or NPA concentration. However, patients who received the largest number of transfusions on the day of surgery had significantly lower NPA concentrations than patients who required no transfusion.

CONCLUSIONS

These results indicate that the NPA concentration more accurately reflects the antithrombotic effect of warfarin than does prothrombin time and may be superior in monitoring prophylactic oral anticoagulation.
Exercise conditioning in older coronary patients. Submaximal lactate response and endurance capacity.
Authors: Ades P A , Waldmann M L , Poehlman E T , Gray P , Horton E D , Horton E S , LeWinter M M
Published: June 2012

BACKGROUND

Older coronary patients are at high risk of cardiac disability. Exercise conditioning programs have been demonstrated to improve functional capacity, particularly in younger coronary patients. In this study, the effects of aerobic conditioning on submaximal and maximal indicators of exercise performance were examined in 45 older coronary patients.

METHODS AND RESULTS

Forty-five patients (mean age, 69 +/- 6 years; range, 62 to 82 years) entered 3-month and 12-month (n = 11) endurance training programs. Training effects were assessed during an exhaustive submaximal exercise protocol with measurement of endurance time, serum lactate, perceived exertion, and expired ventilatory measures. Exhaustive endurance time increased by more than 40% (30 +/- 10 to 41 +/- 10 minutes), with associated decreases in serum lactate, perceived exertion, minute ventilation, heart rate, and systolic blood pressure during steady-state exercise. Respiratory exchange ratio during steady-state exercise, an indicator of substrate utilization, decreased, indicating a shift toward greater use of free fatty acids as a metabolic fuel. In a subset of 10 patients, percent body fat was decreased (32 +/- 8% to 29 +/- 10%) over a period of 3 months.

CONCLUSIONS

Older coronary patients respond to aerobic conditioning with remarkable improvements in submaximal endurance capacity, out of proportion to the more modest increases in VO2max. Activities that were exhaustive before training became sustainable for extended periods of time at a lower perceived exertion. Measurements of serum lactate, respiratory exchange ratio, and ventilation during steady-state exercise document that at an identical absolute work load after conditioning, exercise is performed using aerobic substrate to a greater degree, and ventilatory response to a given work load is lessened.
Probucol decreases neointimal formation in a swine model of coronary artery balloon injury. A possible role for antioxidants in restenosis.
Authors: Schneider J E , Berk B C , Gravanis M B , Santoian E C , Cipolla G D , Tarazona N , Lassegue B , King S B
Published: June 2012

BACKGROUND

Restenosis after percutaneous transluminal coronary angioplasty is the major limitation of the long-term success of this procedure. The process of restenosis is similar to an accelerated form of atherosclerosis. Thus, therapeutic interventions that limit the progression and initiation of atherosclerosis may be beneficial in the treatment of restenosis. One such intervention is the antioxidant drug probucol, which has demonstrated benefit in animal models of atherosclerosis.

METHODS AND RESULTS

Twenty-six female domestic swine were divided into three study groups (control, n = 9; low-dose probucol, n = 9; high-dose probucol, n = 8) before oversized balloon injury of the left anterior descending and left circumflex coronary arteries. Probucol (1 g/d, low-dose group; 2 g/d, high-dose group) was administered 2 days before balloon injury and was continued until the swine were killed 2 weeks after balloon injury. Morphometric analysis of the injured arteries included the intimal area (square millimeters), maximal intimal thickness (millimeters), and residual lumen (ratio of luminal to intimal plus luminal area). Treatment with high-dose probucol significantly reduced neointimal formation compared with control animals (decreases of 36% in intimal area, P = .007; 20% in maximal intimal thickness, P = NS; and an increase of 15% in residual lumen, P = .02).

CONCLUSIONS

The major finding of this study is that the antioxidant drug probucol reduces neointimal formation after oversized balloon injury in a swine model of restenosis. This suggests that active oxygen species may play a role in restenosis.
Chronic atrial fibrillation and stroke in paced patients with sick sinus syndrome. Relevance of clinical characteristics and pacing modalities.
Authors: Sgarbossa E B , Pinski S L , Maloney J D , Simmons T W , Wilkoff B L , Castle L W , Trohman R G
Published: June 2012

BACKGROUND

The goal of the report was to study the long-term incidence and the independent predictors for chronic atrial fibrillation and stroke in 507 paced patients with sick sinus syndrome, adjusting for differences in baseline clinical variables with multivariate analysis.

METHODS AND RESULTS

From 1980 to 1989, we implanted 376 dual-chamber, 19 atrial, and 112 ventricular pacemakers to treat patients with sick sinus syndrome. After a maximum follow-up of 134 months (mean: 59 +/- 38 months for chronic atrial fibrillation, 65 +/- 37 months for stroke), actuarial incidence of chronic atrial fibrillation was 7% at 1 year, 16% at 5 years, and 28% at 10 years. Independent predictors for this event, from Cox's proportional hazards model, were history of paroxysmal atrial fibrillation (P < .001; hazard ratio [HR] = 16.84), use of antiarrhythmic drugs before pacemaker implant (P < .001; HR = 2.25), ventricular pacing mode (P = .003; HR = 1.98), age (P = .005; HR = 1.03), and valvular heart disease (P = .008; HR = 2.05). For patients with preimplant history of paroxysmal atrial fibrillation, independent predictors were prolonged episodes of paroxysmal atrial fibrillation (P < .001; HR = 2.56), long history of paroxysmal atrial fibrillation (P = .004; HR = 2.05), ventricular pacing mode (P = .025; HR = 1.69), use of antiarrhythmic drugs before pacemaker implant (P = .024; HR = 1.71), and age (P = .04; HR = 1.02). Actuarial incidence of stroke was 3% at 1 year, 5% at 5 years, and 13% at 10 years. Independent predictors for stroke were history of cerebrovascular disease (P < .001; HR = 5.22), ventricular pacing mode (P = .008; HR = 2.61), and history of paroxysmal atrial fibrillation (P = .037; HR = 2.81).

CONCLUSIONS

Development of chronic atrial fibrillation and stroke in paced patients with sick sinus syndrome are strongly determined by clinical variables and secondarily by the pacing modality. Ventricular pacing mode predicts chronic atrial fibrillation in patients with preimplant paroxysmal atrial fibrillation but not in those without it.
Application of color Doppler flow mapping to calculate effective regurgitant orifice area. An in vitro study and initial clinical observations.
Authors: Vandervoort P M , Rivera J M , Mele D , Palacios I F , Dinsmore R E , Weyman A E , Levine R A , Thomas J D
Published: June 2012

BACKGROUND

Analogous to stenotic valve area in the assessment of valvular stenosis, regurgitant orifice area (ROA) represents a fundamental parameter to assess valvular insufficiency. However, this parameter has not been routinely available up to now. In this study, we introduce the concept and provide the methodology to calculate regurgitant orifice area noninvasively, based on the analysis of the proximal flow convergence zone.

METHODS AND RESULTS

In an in vitro study, we showed the feasibility and the accuracy of calculating effective ROA by the proximal flow convergence method throughout a range of driving pressures. The calculated and true ROA showed an excellent correlation with r = .992, delta ROA = -1.4 +/- 2.9 mm2. We then applied this concept clinically in 77 patients with mitral regurgitation and showed a very good correlation between effective ROA calculated by the proximal flow convergence method and calculated by the Doppler echocardiographic method: r = .95, delta ROA = -0.2 +/- 3.9 mm2. The ROA also correlated very well with Doppler echocardiographic-derived regurgitant stroke volume (r = .93) and regurgitant fraction (r = .82). In a subgroup of 20 patients who underwent invasive evaluation, the calculated effective ROA also correlated well with the angiographic grade of mitral regurgitation (rho = .81).

CONCLUSIONS

We conclude that effective ROA represents unique information on the severity of a regurgitant lesion and can easily be calculated by the proximal flow convergence method. This new parameter should enhance our understanding and improve the serial assessment of valvular regurgitation.
Downregulation of c-myc expression by antisense oligonucleotides inhibits proliferation of human smooth muscle cells.
Authors: Shi Y , Hutchinson H G , Hall D J , Zalewski A
Published: June 2012

BACKGROUND

Proliferation of smooth muscle cells (SMCs) plays an important role in vascular pathobiology, being involved in the development of coronary restenosis and atherosclerosis. The activation of nuclear proto-oncogenes appears to be a final common pathway onto which various mitogenic signals coverage. Accordingly, we attempted to determine whether the activation of the c-myc nuclear proto-oncogene is essential for human SMC proliferation and explored the possibility of inhibiting their growth using antisense oligonucleotides directed against c-myc messenger RNA (mRNA).

METHODS AND RESULTS

Proliferation of human SMCs was associated with an increase in c-myc mRNA expression after growth stimulation. Using 15-mer phosphorothioate oligonucleotides (oligomers), we tested their growth-inhibitory effect in SMCs in vitro. Antisense oligomers directed against the translation initiation region of the human c-myc gene exhibited a significant antiproliferative effect, whereas sense and mismatched oligomers did not inhibit the growth. The growth-inhibitory effect of c-myc antisense oligomers was dose dependent and preventable by an excess of sense oligomers. Furthermore, growth inhibition of SMCs treated with c-myc antisense oligomers was associated with a marked decrease in the c-myc mRNA level. Phosphorothioate oligomers remained stable in medium containing 20% serum and were detectable in SMCs as early as 1 hour after cell exposure. Intact oligomers rapidly accumulated intracellularly and persisted within human SMCs for at least 16 hours.

CONCLUSIONS

c-myc antisense oligomers reduced c-myc expression and produced a significant growth inhibition of human SMCs, indicating an important role of c-myc gene activation in the process of SMC proliferation. Furthermore, extracellular stability and rapid cellular uptake provide the basis for future studies assessing the therapeutic role of the c-myc antisense approach in reducing SMC proliferation in the process of vascular restenosis.
Cardiac stress protein elevation 24 hours after brief ischemia or heat stress is associated with resistance to myocardial infarction.
Authors: Marber M S , Latchman D S , Walker J M , Yellon D M
Published: June 2012

BACKGROUND

To test the hypothesis that the heat shock response is associated with myocardial salvage, the heat stress protein (HSP) content of cardiac tissue was increased by either ischemic or thermal stress.

METHODS AND RESULTS

Rabbits were divided into four groups. Ischemic pretreatment (n = 15) comprised four 5-minute episodes of coronary ligation separated by 10 minutes of reperfusion. The corresponding control group (n = 21) underwent surgical preparation without coronary ligation. Thermal pretreatment (n = 16) involved whole-body temperature elevation to 42 degrees C for 15 minutes; corresponding controls (n = 15) were treated with anesthetic alone. Twenty-four hours later, hearts were removed for HSP estimation or infarct size assessment after a 30-minute coronary ligation. Myocardial HSP72 content assessed by Western blotting was elevated by both ischemic and thermal pretreatments (2.5 +/- 0.2 units, n = 4, and 2.8 +/- 0.3 units, n = 4, mean +/- SEM; P = NS, respectively) compared with the corresponding control groups (1.0 +/- 0.3, n = 4, P < or = .01 and 0.3 +/- 0.1, n = 4, P < or = .01, respectively). HSP60 was preferentially elevated by ischemic pretreatment. After a 30-minute coronary occlusion and 120 minutes of reperfusion, ischemic and thermal pretreatments limited infarct size as a percentage of the volume at risk by 28.8 +/- 5.2% vs 52.0 +/- 5.2%, P < or = .01 and 32.8 +/- 3.8% vs 56.9 +/- 6.5%, P < or = .01, respectively.

CONCLUSIONS

Myocardial stress protein induced by either sublethal thermal or ischemic injury is associated with myocardial salvage. Our findings suggest that stress protein elevation, rather than the nonspecific effects of thermal or ischemic stress, may be responsible for the myocardial protection seen in this model. Our observations may have important implications regarding myocardial adaptation to brief periods of ischemia.
Streptozotocin-induced non-insulin-dependent diabetes protects the heart from infarction.
Authors: Liu Y , Thornton J D , Cohen M V , Downey J M , Schaffer S W
Published: June 2012

BACKGROUND

The vulnerability of the myocardium of a diabetic animal to an ischemic insult is controversial. To address this issue, streptozotocin-induced non-insulin-dependent diabetes (NIDD) was induced in rats, and the effects of regional myocardial ischemia were assessed by measuring infarct size.

METHODS AND RESULTS

Open-chest rats with NIDD and age-matched control rats underwent 30 or 45 minutes of regional ischemia and 2-hour reperfusion. Infarct size was measured by tetrazolium. Control rats had 32.0 +/- 3.3% infarction of the risk zone after a 30-minute coronary occlusion, whereas NIDD rats had significantly smaller infarcts (11.5 +/- 3.1% of the risk area, P < .005). When ischemic time was extended to 45 minutes, infarct size in control animals averaged 57.9 +/- 6.2%, whereas only 37.3 +/- 5.6% of ischemic myocardium was infarcted in NIDD rats (P < .05). In a subset NIDD group, rats experienced a period of ischemic preconditioning (three cycles of 5-minute ischemia/5-minute reperfusion) before 45-minute ischemia. Infarct size in these rats averaged only 6.9 +/- 3.0% (P < .01 vs nonpreconditioned NIDD rats with 45-minute coronary occlusions). Collateral flow was measured in NIDD rat hearts with radioactive microspheres. Collateral flow was < 1% of normal myocardial blood flow.

CONCLUSIONS

We conclude that NIDD protects the heart from infarction and that this protection is not related to the development of coronary collaterals. Furthermore, preconditioning can further protect the NIDD heart.
Regional differences in function within noninfarcted myocardium during left ventricular remodeling.
Authors: Kramer C M , Lima J A , Reichek N , Ferrari V A , Llaneras M R , Palmon L C , Yeh I T , Tallant B , Axel L
Published: June 2012

BACKGROUND

The mechanisms of ventricular enlargement and dysfunction during postinfarct remodeling remain largely unknown. Although global left ventricular architectural changes after myocardial infarction are well documented, differences in function between adjacent and remote noninfarcted myocardium during left ventricular remodeling have not been investigated. These functional differences may relate to regional differences in wall stress during contraction and may contribute to chamber enlargement and global dysfunction after infarction.

METHODS AND RESULTS

Anteroapical infarcts were produced in seven sheep by ligation of the mid left anterior descending coronary artery and second diagonal branch at thoracotomy. Magnetic resonance short-axis and long-axis images tagged by spatial modulation of magnetization were obtained before and 1 week, 8 weeks, and 6 months after infarction. Left ventricular volumes, mass, ejection fraction, and lengths of infarcted and noninfarcted segments were measured. Circumferential and longitudinal shortening in the subendocardium and subepicardium, wall thickness, and histopathology were assessed in infarcted segments and regions adjacent to and remote from the infarct border. We found that a difference in circumferential and longitudinal segmental shortening between adjacent and remote noninfarcted myocardium present at 1 week persisted up to 6 months after myocardial infarction. However, partial improvement of function in adjacent regions occurred during infarct healing between 1 and 8 weeks after infarction. Left ventricular volume increased up to 6 months after infarction, out of proportion to the concomitant eccentric hypertrophy, whereas the ejection fraction fell. Left ventricular dilatation late in the remodeling process was secondary to lengthening of noninfarcted segments, which were free of significant fibrosis.

CONCLUSIONS

Left ventricular dilatation and eccentric hypertrophy during remodeling are associated with persistent differences in segmental function between adjacent and remote noninfarcted regions. These functional differences may reflect increased wall stress in adjacent noninfarcted regions and contribute to the global dilatation and dysfunction characteristic of left ventricular remodeling after infarction.
Cardiac noradrenergic nerve terminal abnormalities in dogs with experimental congestive heart failure.
Authors: Himura Y , Felten S Y , Kashiki M , Lewandowski T J , Delehanty J M , Liang C S
Published: June 2012

BACKGROUND

We have shown previously that norepinephrine (NE) uptake activity is reduced in the failing right ventricle of animals with right heart failure (RHF) produced by tricuspid avulsion and progressive pulmonary constriction. However, it is unknown whether this defect in neuronal NE uptake is related to reduction of noradrenergic nerve terminals or whether these changes also occur in animals with left heart failure (LHF). It is also unknown whether increased NE release in heart failure contributes to the noradrenergic nerve abnormalities.

METHODS AND RESULTS

We measured myocardial NE content. NE uptake function, and noradrenergic nerve profiles in dogs with either RHF or LHF induced by rapid ventricular pacing. NE uptake activity was measured using [3H]NE, and noradrenergic nerve profiles were visualized by glyoxylic acid (SPG)-induced histofluorescence and tyrosine hydroxylase immunocytochemical staining. To study the effects of excess NE, we exposed normal dogs to 8 weeks of chronic NE infusion using subcutaneous osmotic minipumps. RHF and LHF animals exhibited reduced myocardial contractile function and congestive heart failure, as evidence by reduced cardiac output and elevated right atrial pressure. However, unlike that in LHF, left atrial pressure was not increased in RHF. The animals also showed an increase in plasma NE and a decrease in cardiac NE. In addition, SPG-induced histofluorescence correlated significantly with NE uptake activity (r = .712, P < .001) and tyrosine hydroxylase immunoreactive profiles (r = .569, P < .001) in the right ventricles of RHF dogs and in both ventricles of LHF dogs. The numbers of catecholaminergic profiles and tyrosine hydroxylase profiles significantly correlated with cardiac filling pressures. Chronic infusion of NE decreased heart rate in normal dogs but had no effect on either mean aortic pressure or left atrial pressure; like heart failure, it resulted in significant decreases in myocardial NE uptake activity and numbers of SPG-induced catecholaminergic histofluorescence and immunoreactive tyrosine hydroxylase profiles.

CONCLUSIONS

Myocardial NE uptake activity was reduced only in the failing ventricles with elevated filling pressure in RHF and LHF. These changes probably were caused by loss of noradrenergic nerve terminals in the failing ventricles, as evidenced by the reductions of catecholaminergic histofluorescence and tyrosine hydroxylase immunostained profiles. Furthermore, since similar reductions of myocardial NE uptake and noradrenergic nerve profiles could be produced by chronic NE infusion in normal dogs, elevated NE levels may play a role in the development of cardiac noradrenergic nerve abnormalities in congestive heart failure.
Coexistence of functioning beta 1- and beta 2-adrenoceptors in single myocytes from human ventricle.
Authors: del Monte F , Kaumann A J , Poole-Wilson P A , Wynne D G , Pepper J , Harding S E
Published: June 2012

BACKGROUND

Both beta 1- and beta 2-adrenoceptors (beta 1 AR and beta 2 AR) are present in human ventricle. This study was designed to determine whether the two subtypes contribute to contraction in single myocytes from human heart.

METHODS AND RESULTS

(-)-Epinephrine increased the contraction amplitude and velocity of single myocytes isolated from the ventricles of failing and nonfailing human hearts. Concentration-response curves to (-)-epinephrine were constructed in the presence and absence of selective antagonists for beta 1 AR (CGP 20712A) and beta 2 AR (ICI 118,551). Responses to (-)-epinephrine were antagonized to a variable degree by the blockers, suggesting heterogeneous contribution of beta 1AR and beta 2AR among cells. The most common response in single myocytes was that ICI 118,551 (50 nmol/L) shifted the concentration-response curve less than 10-fold: this was lower than the 100-fold shift expected for a pure beta 2AR effect. Inclusion of CGP 20712A (300 nmol/L) with ICI 118,551 shifted the (-)-epinephrine curve still further. These observations suggest that both beta 1AR and beta 2AR contribute to the increase in contraction amplitude with (-)-epinephrine in this group of myocytes. When 300 nmol/L CGP 20712A was present as the sole antagonist, only a marginal shift of the concentration-response curve for (-)-epinephrine was usually observed, indicating that beta 1AR were not mediating the effect of these low concentrations of (-)-epinephrine. Both beta 1AR and beta 2AR mediated a considerable abbreviation of the time to peak contraction and time to 50% relaxation in the single cells.

CONCLUSIONS

beta 1AR and beta 2AR coexist and function on human ventricular myocytes. At low (-)-epinephrine concentrations, contractile responses are predominantly mediated by beta 2AR rather than beta 1AR in myocytes from failing hearts.
Electrocardiographic diagnosis of postinfarction regional pericarditis. Ancillary observations regarding the effect of reperfusion on the rapidity and amplitude of T wave inversion after acute myocardial infarction.
Authors: Oliva P B , Hammill S C , Edwards W D
Published: June 2012

BACKGROUND

The ECG recognition of diffuse pericarditis following acute myocardial infarction has been based on changes of the ST segment and, to a lesser extent, alterations of the PQ segment. No ECG criteria exist for the diagnosis of postinfarction regional pericarditis. Recently, it was observed that the T wave evolution follows an atypical pattern before fatal free wall rupture and that this pattern is due to the associated pericarditis. Therefore, this study was conducted on 200 patients with acute myocardial infarction to further elucidate the sensitivity and specificity of the atypical T wave changes in patients with regional postinfarction pericarditis without rupture and to assess the affect of lytic treatment on the rapidity and amplitude of postinfarction T wave evolution.

METHODS AND RESULTS

An analysis of the clinical courses and serial ECGs of 200 consecutive patients with acute myocardial infarction was performed. Among 43 patients with postinfarction pericarditis, the pattern of T wave evolution consistently differed from the customary postinfarction pattern of T wave evolution. This unusual evolutionary course was expressed as either persistently positive T waves 48 or more hours after infarction (67%) or premature, gradual reversal of inverted T waves to positive deflections (33%). The sensitivity and specificity of these T wave alterations were 100% and 77%, respectively. The only other processes identified that caused this type of postinfarction T wave evolution were cardiopulmonary resuscitation, reinfarction, and very small infarcts. Both reperfusion, as judged by the creatine kinase-MB curve, and patency, as assessed by the angiogram, were correlated with the rapidity and depth of T wave inversion. Ninety percent of patients with reperfusion attained a maximum T wave negativity of 3 mm or more within 48 hours after the onset of chest pain in the lead that initially displayed the greatest ST segment elevation. Seventy-six percent of patients without reperfusion attained a maximum negativity of 2 mm or less within 72 hours. Thus, like the ST segment, accelerated evolution and deepening of the T wave may be noninvasive markers of reperfusion.

CONCLUSIONS

First, premature reconcordancy of the ST segment and T wave after acute myocardial infarction is a sensitive, reasonably specific, and easily recognizable ECG manifestation of postinfarction regional pericarditis. Second, reperfusion is associated with accelerated evolution and deepening of the T waves following acute myocardial infarction.
Slow conduction in the infarcted human heart. 'Zigzag' course of activation.
Authors: de Bakker J M , van Capelle F J , Janse M J , Tasseron S , Vermeulen J T , de Jonge N , Lahpor J R
Published: June 2012

BACKGROUND

Ventricular tachycardias occurring in the chronic phase of myocardial infarction are caused by reentry. Areas of slow conduction, facilitating reentry, are often found in the infarcted zone. The purpose of this study was to elucidate the mechanism of slow conduction in the chronic infarcted human heart.

METHODS AND RESULTS

Spread of activation was studied in infarcted papillary muscles from hearts of patients who underwent heart transplantation because of infarction. Recordings were carried out on 10 papillary muscles that were superfused in a tissue bath. High-resolution mapping was performed in areas revealing slow conduction. Activation delay between sites perpendicular to the fiber direction and 1.4 mm apart could be as long as 45 milliseconds. Analysis of activation times revealed that activation spread in tracts parallel to the fiber direction. Conduction velocity in the tracts was between 0.6 and 1 m/s. Although tracts were separated from each other over distances up to 8 mm, they often connected with each other at one or more sites, forming a complex network of connected tracts. In this network, wave fronts could travel perpendicular to the fiber direction. Separation of tracts was due to collagenous septa. At sites where tracts were interconnected, the collagenous barriers were interrupted.

CONCLUSIONS

Slow conduction perpendicular to the fiber direction in infarcted myocardial tissue is caused by a "zigzag" course of activation at high speed. Activation proceeds along pathways lengthened by branching and merging bundles of surviving myocytes ensheathed by collagenous septa.
Height and incidence of cardiovascular disease in male physicians.
Authors: Hebert P R , Rich-Edwards J W , Manson J E , Ridker P M , Cook N R , O'Connor G T , Buring J E , Hennekens C H
Published: June 2012

BACKGROUND

An inverse association between height and risk of coronary heart disease (CHD) has been reported in several case-control and cohort studies, but the reasons for the association remain uncertain. We evaluated this association among 22,071 male physicians, a population homogeneous for high educational attainment and socioeconomic status in adulthood.

METHODS AND RESULTS

The study population was comprised of participants in the Physicians' Health Study, a randomized, double-blind, placebo-controlled trial of low-dose aspirin and beta-carotene in the primary prevention of cardiovascular disease and cancer among US male physicians, aged 40 to 84 years, in 1982. Participants were classified into five height categories at study entry, from shortest to tallest, and were followed an average of 60.2 months to determine the incidence of myocardial infarction (MI), stroke, and death from cardiovascular disease. Men in the tallest (> or = 73 in. or 185.4 cm) compared with the shortest (< or = 67 in. or 170.2 cm) height category had a 35% lower risk of MI (relative risk, 0.65; 95% confidence interval, 0.44 to 0.99; P = .04), after adjusting for known cardiovascular risk factors. Further, a marginally significant inverse trend (P trend = .05) across the height categories was observed. Although the relationship was not strictly linear, for every inch of added height, there was an approximate 2% to 3% decline in risk of MI. In contrast, men in the tallest compared with the shortest height category had only small and nonsignificant decreases in risk of stroke and cardiovascular death. While no significant trend in risks of these end points across the height categories was observed, the numbers of events for these end points were far less than for MI, and thus the confidence intervals were wide.

CONCLUSIONS

These data indicate that height is inversely associated with subsequent risk of MI. At this time, a few mechanisms are plausible, but none are convincing. Other epidemiological and basic research efforts are needed to explore a variety of physiological correlates of height that may be responsible for mediating the height-MI association. In the meantime, while height is not modifiable, it is easy to measure and may be useful to evaluate CHD disease risk profiles and target lifestyle interventions.
Role of preclinical cardiovascular disease in the evolution from risk factor exposure to development of morbid events.
Authors: Devereux R B , Alderman M H
Published: June 2012

Conventional risk factors (especially high arterial pressure, elevated cholesterol and glucose levels, and cigarette smoking) are useful predictors of morbid atherosclerotic and hypertensive events, and their control variably reduces the incidence of events. However, both the ability to predict risk and the ability to reduce it by modification of established risk factors are limited. These limitations occur in part because the progression from risk factor exposure to morbid events depends on the variable likelihood that individuals exposed to the same risk factors will progress through two stages: the development of asymptomatic or "preclinical" anatomic and functional cardiovascular disease in response to standard risk factors and other variables, and the precipitation of morbid events by progression of preclinical disease or by the action of additional "triggering" mechanisms in the presence of preclinical disease. Advances in diagnostic methodology now make possible accurate noninvasive detection in many asymptomatic individuals of preclinical disease such as left ventricular hypertrophy, carotid atherosclerosis, and renal dysfunction. Progress in elucidating stimuli to left ventricular hypertrophy and systemic atherosclerosis suggests that focusing research separately on these two stages of disease evolution is a fruitful strategy. The closer relation of measures of preclinical disease than risk factors with the subsequent risk of complications indicates that their detection improves clinical risk stratification. However, critical testing of whether clinical outcome is improved or treatment cost is lowered by basing antihypertensive or antihyperlipidemic treatment decisions in part on the presence of preclinical cardiovascular disease is needed before this strategy is adopted on a widespread scale.
Angiographic-pathologic correlations after elective percutaneous transluminal coronary angioplasty.
Authors: Naruko T , Ueda M , Becker A E , Tojo O , Teragaki M , Takeuchi K , Takeda T
Published: June 2012

BACKGROUND

The local effect of coronary angioplasty is evaluated on the basis of postangioplasty angiograms. Smooth-walled dilation is considered to represent minimal or no injury, whereas intraluminal haziness corresponds with wall laceration. This study correlates the preangioplasty and postangioplasty angiograms with the histopathology of the target sites.

METHODS AND RESULTS

The study includes 12 patients, each undergoing an elective procedure, and covers 19 angioplasty sites. Smooth-walled dilation and intraluminal haziness were not mutually exclusive. The angiograms were interpreted as smooth-walled dilation (n = 3), smooth-walled dilation with intraluminal haziness (n = 4), intraluminal and extraluminal haziness (n = 5), extraluminal dissection (n = 5), spiraltype dissection (n = 1), and aneurysm (n = 1). The histology of the arterial segments revealed wall laceration in all. Smooth-walled dilation without intraluminal haziness correlated with laceration limited to the intima in two, but with medial injury in one. Smooth-walled dilation with intraluminal haziness correlated with laceration limited to the intima in two and with medial injury in two. Intraluminal and extraluminal haziness corresponded with extensive laceration with deep involvement of the media in each. Extraluminal dissection correlated with a dissection along the shoulder area of the plaque, creating a broad-based flap. The spiral-type dissection corresponded with a true dissection into the plaque-free media. The aneurysm correlated with partial washout of an atherosclerotic plaque.

CONCLUSIONS

The angiographic image of intraluminal and extraluminal haziness indicates extensive medial laceration. Smooth-walled dilation, with or without intraluminal haziness, is not a reliable indicator. The study emphasizes the need to reconsider the interpretations of postangioplasty coronary angiograms.