bluuebunny/crossref_metadata_2025 huggingface dataset:
Endothelium-derived relaxing factor and protection against contractions induced by histamine and serotonin in the human internal mammary artery and in the saphenous vein.
Authors: Yang Z H , Diederich D , Schneider K , Siebenmann R , Stulz P , von Segesser L , Turina M , Bühler F R , Lüscher T F
Published: June 2011

We investigated the release of endothelium-derived relaxing factor (EDRF) in response to serotonin and histamine in the human internal mammary artery and saphenous vein. The arteries and veins were obtained intraoperatively and were suspended in organ chambers to record isometric tension. In mammary arteries, histamine (10(-8) to 3 X 10(-6) M) induced relaxations in rings with (70 +/- 5%, IC50, 6.5 +/- 0.2) but not without endothelium (p less than 0.005 for rings with compared with those without endothelium, n = 7-10). The response was inhibited by methylene blue or hemoglobin, but not meclofenamate, and, therefore, EDRF was delineated as the mediator. Because chlorpheniramine but not cimetidine inhibited the response, EDRF was released by the H1-histaminergic receptor (n = 5-8). In contrast, in saphenous veins, histamine caused only weak or absent endothelium-dependent relaxations, but contractions were enhanced in rings with endothelium (p less than 0.05, n = 6). Serotonin did not induce endothelium-dependent relaxations, but contractions were markedly greater in veins compared with arteries (p less than 0.005, n = 6). The endothelium inhibited the maximal contraction to serotonin in arteries (p less than 0.034) but not in veins. Thus, EDRF protects against contractions induced by histamine and serotonin in the mammary artery but not in the saphenous vein. This may be important for improved graft function and patency of the artery compared with that of the vein.
Percutaneous catheter modification of the atrioventricular node. A potential cure for atrioventricular nodal reentrant tachycardia.
Authors: Epstein L M , Scheinman M M , Langberg J J , Chilson D , Goldberg H R , Griffin J C
Published: June 2011

Our purpose was to describe a technique of atrioventricular (AV) node modification for patients with drug refractory AV nodal reentrant tachycardia (AVNRT). Nine patients (mean age, 45 +/- 20; range, 14-82) with recurrent drug refractory AVNRT (n = 8) or sudden cardiac death thought to be precipitated by AVNRT (n = 1) underwent a percutaneous catheter procedure to modify AV nodal function. The area between the electrode recording the maximal His-bundle electrogram and the ostium of the coronary sinus was divided into three zones. Perinodal direct current shocks of 100-300 J were delivered to one (n = 2), two (n = 3), or three (n = 4) zones without complications. The procedure endpoints were modification of AV conduction (either first degree AV block or complete retrograde ventriculo-atrial [VA] block) and failure to induce AVNRT before or after isoproterenol and/or atropine administration. Six of nine patients (67%) have had no inducible or spontaneous AVNRT over a mean follow-up of 12.3 +/- 4.1 months (range, 4.5-17). One of the six underwent repeat, successful modification, because AVNRT was inducible at restudy 2 days after the initial procedure. AVNRT recurred in three patients (33%), one early (3 days) and two late (3-4 months). Two of these patients underwent complete ablation of the AV junction and permanent pacemaker placement, whereas one is controlled with drug therapy. Therefore, AV nodal modification resulted in tachycardia control without antiarrhythmic drugs in six of nine (67%) and obviated the need for complete AV junctional ablation in seven of nine patients (78%). Elimination of AVNRT appears to result from either block in the retrograde fast pathway or modification of the antegrade slow pathway, such that AVNRT cannot be sustained. Additional findings suggest that an atrio-Hisian accessory connection may not be involved in AVNRT in some of these patients. Percutaneous catheter AV nodal modification appears to be a promising technique for treatment of refractory AVNRT and may obviate need for complete AV junctional ablation in a substantial number of patients with drug/pacemaker refractory AVNRT.
Induction of vasospastic attacks despite digital nerve block in Raynaud's disease and phenomenon.
Authors: Freedman R R , Mayes M D , Sabharwal S C
Published: June 2011

Using a combination of environmental and local cooling, we induced vasospastic attacks of Raynaud's phenomenon in nine of 11 patients with idiopathic Raynaud's disease and in eight of 10 patients with scleroderma. Attacks were defined as occurring if two of the possible three color changes (pallor, cyanosis, and rubor) occurred, and serial photographs were scored by three independent raters. Two fingers on one hand were anesthetized by local injection of lidocaine, and the effectiveness of nerve blocks was verified by plethysmography. The frequency of vasospastic attacks in nerve-blocked fingers was not significantly different from that in the corresponding intact fingers on the contralateral hand. These findings show that the vasospastic attacks of Raynaud's disease and phenomenon can occur without the involvement of efferent digital nerves and argue against the etiologic role of sympathetic hyperactivity.
Recurrent ischemia without warning. Analysis of risk factors for in-hospital ischemic events following successful thrombolysis with intravenous tissue plasminogen activator.
Authors: Ellis S G , Topol E J , George B S , Kereiakes D J , Debowey D , Sigmon K N , Pickel A , Lee K L , Califf R M
Published: June 2011

Ischemic events after successful thrombolysis have been reported to occur in 18-32% of patients treated for acute myocardial infarction with thrombolytic therapy, and previous studies in which patients received streptokinase suggest that risk of early recurrent ischemia is closely related to the presence of a high-grade residual stenosis. If these events are predictable after intravenous recombinant tissue-plasminogen activator (rt-PA) thrombolytic therapy, then further intervention after its use could be targeted at selected patients. One-hundred ninety-two patients from the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) I and TAMI III trials had successful rt-PA-mediated thrombolysis without immediate coronary angioplasty (PTCA). One-hundred seventy-four of these patients (92%) had prehospital discharge angiography. The mean age was 56 +/- 11 years; 81% were men; the infarct-related artery was the left anterior descending in 76 (39.8%), the left circumflex in 24 (12.6%), and the right coronary artery in 91 (47.6%). Thrombolysis with rt-PA resulted in a residual 73 +/- 13% diameter and 0.95 +/- 0.51 mm stenosis by quantitative coronary arteriography, and Thrombolysis in Myocardial Infarction (TIMI) flow grade 2 in 59.2% and 3 in 40.8% of stenoses as assessed on angiograms obtained 90 minutes after the initiation of rt-PA therapy. Recurrent ischemic events (ischemia requiring emergency percutaneous transluminal coronary angioplasty or urgent bypass surgery, reocclusion of the infarct-related artery, or cardiac death) occurred in 41 patients (21.3%).(ABSTRACT TRUNCATED AT 250 WORDS)
Medical compared with surgical management of unstable angina. 5-year mortality and morbidity in the Veterans Administration Study.
Authors: Parisi A F , Khuri S , Deupree R H , Sharma G V , Scott S M , Luchi R J
Published: June 2011

We evaluated medical in comparison to surgical plus medical (surgical) treatment of unstable angina using a prospective randomized protocol that stratified patients by clinical presentation and by invasive evaluation of left ventricular (LV) function. Clinical presentations were as follows--type 1: progressive or new onset angina relieved by medication; type 2: prolonged bouts of angina poorly or incompletely relieved by medication. Abnormal LV function was arbitrarily defined as ejection fraction less than 0.50 or LV end-diastolic pressure 16 mm Hg or more. Of 468 patients, 237 were assigned to medical and 231 to surgical therapy. There were 374 type 1 and 94 type 2 patients. LV function was normal in 334 and abnormal in 134 patients. Compared with results at 24 months, this 60-month follow-up study showed important differences in survival for patients with three-vessel disease: 75% for medical and 89% for surgical patients (p less than 0.02). The cumulative 5-year rate of repeat hospitalizations for cardiac reasons was less with surgical patients for either clinical presentation. For type 1, medical patients had a 56% rate, and surgical patients had a 42% rate (p = 0.004). For type 2, medical patients had a 62% rate, and surgical patients had a 43% rate (p = 0.05). Overall mortality did not differ between the two treatments, and this remained true in type 1 versus type 2 patients and in those with normal versus abnormal LV function. However, regression analysis of medical and surgical groups with ejection fraction as a continuous variable showed that mortality of medical patients depended on ejection fraction (p = 0.004), whereas the mortality of surgical patients did not (p = 0.76), and survival in the surgical group was higher in the lowest ejection fraction tercile-73% for medical and 86% for surgical patients, p = 0.03. We conclude that surgery improves survival in patients with three-vessel disease and leads to fewer subsequent hospitalizations for cardiac reasons. An impaired ejection fraction had an adverse impact on survival of medical patients but not on surgical patients, and mortality in surgical patients was improved compared with medical patients in the lowest ejection fraction tercile.
Histopathology of primary pulmonary hypertension. A qualitative and quantitative study of pulmonary blood vessels from 58 patients in the National Heart, Lung, and Blood Institute, Primary Pulmonary Hypertension Registry.
Authors: Pietra G G , Edwards W D , Kay J M , Rich S , Kernis J , Schloo B , Ayres S M , Bergofsky E H , Brundage B H , Detre K M
Published: June 2011

Qualitative and quantitative studies were performed on pulmonary blood vessels in lung tissue obtained by biopsy, pneumonectomy, or autopsy from 58 patients in the Registry of Primary Pulmonary Hypertension sponsored by the Heart, Lung, and Blood Institute of the National Institutes of Health. In 49 patients (84%), the hypertensive vascular disease involved predominantly or exclusively muscular pulmonary arteries and arterioles. In each of these 49 patients, pulmonary artery medial hypertrophy was observed, and in 48 patients, it was also associated with intimal or luminal lesions. On the basis of the predominant histopathologic features, 25 of the 48 patients were classified as having pulmonary arteriopathy with plexiform lesions characterized by a combination of concentric laminar intimal fibrosis, eccentric intimal fibrosis, and plexiform lesions; in nine of these 25, recanalized thrombi were also present. Pulmonary arteriopathy with thrombotic lesions, defined by the presence of both eccentric intimal fibrosis and recanalized thrombi but without plexiform lesions, was observed in 19 patients. Intimal fibrosis, either concentric or eccentric, without plexiform or thrombotic lesions was found in four patients. Among the remaining nine patients in the Registry, pulmonary veno-occlusive disease was present in seven and chronic pulmonary venous hypertension in one. Pulmonary blood vessels were microscopically normal in a lung biopsy specimen from another patient. In general, patients with plexiform lesions and those with veno-occlusive disease had a much poorer prognosis than patients with thrombotic lesions. The present study shows the existence of several distinct histopathologic patterns of pulmonary vascular disease in individuals with primary pulmonary hypertension diagnosed by standardized clinical and laboratory criteria.
The effect of diltiazem on coronary flow reserve in humans.
Authors: Rossen J D , Simonetti I , Marcus M L , Braun P , Winniford M D
Published: June 2011

Calcium channel antagonists have been shown to blunt maximal coronary flow after brief coronary occlusion and during pharmacologic coronary dilation in animals. This property, if present in humans, would result in a reduction in coronary flow reserve in the absence of intrinsic abnormalities of the coronary circulation. A reduction of maximal vasodilator capacity by calcium channel antagonists could also constitute an important anti-ischemic mechanism of action of these agents. To evaluate the effect of calcium channel antagonists on coronary flow reserve in awake humans, we measured coronary flow reserve using the coronary Doppler catheter and intracoronary papaverine at baseline and after diltiazem administered by intravenous (125 or 250 micrograms/kg bolus, 5 micrograms/kg/min infusion, n = 8) or intracoronary (150-600 micrograms bolus, n = 10) routes. Intravenous diltiazem reduced heart rate from 77 +/- 18 to 72 +/- 17 beats/min (mean +/- SD, p less than 0.005) and reduced mean arterial pressure from 96 +/- 11 to 86 +/- 15 mm Hg (p less than 0.005). Intravenous diltiazem resulted in a small decrease in coronary flow reserve (peak-to-resting flow velocity ratio) from 3.9 +/- 1.2 to 3.6 +/- 1.1 (p less than 0.01). After intracoronary diltiazem, mean arterial pressure was unchanged (control 99 +/- 12 mm Hg, diltiazem 97 +/- 13 mm Hg), and heart rate was maintained constant by atrial pacing. Coronary flow reserve was unchanged at 3.8 +/- 0.9 at baseline and after intracoronary diltiazem. Thus, treatment with diltiazem does not invalidate the measurement of coronary flow reserve for diagnostic purposes. Furthermore, these results suggest that attenuation of maximal coronary dilation by diltiazem is not a mechanism responsible for its antianginal effects.
Ventricular sensory endings mediate reflex bradycardia during coronary arteriography in humans.
Authors: Arrowood J A , Mohanty P K , Hodgson J M , Dibner-Dunlap M E , Thames M D
Published: June 2011

It has been suggested that the response to the intracoronary injection of radiographic contrast is reflex in origin and results from stimulation of ventricular sensory endings. Cardiac transplantation results in denervation of the ventricles, and thus, may interrupt the afferent limb of this reflex. In contrast, the recipient sinus node and atrial remnant remain innervated, leaving the efferent cardiac limb of this reflex intact. We hypothesized that if contrast-induced reflex bradycardia and hypotension occurred from stimulation of ventricular chemosensitive endings, then this response would be abolished after cardiac transplantation. To test this hypothesis, we determined the changes in recipient (innervated) and donor (denervated) sinus-node rates (SNR) and mean arterial pressure during selective right (RCA) and left coronary artery (LCA) injection during arteriography in cardiac transplant patients and in patients with intact cardiac innervation. An increase in the recipient SNR was observed in cardiac transplant patients during left and right coronary injections (LCA, 6.6 +/- 1.7 beats/min; RCA, 2.4 +/- 1.4 beats/min) compared with a decrease in the control subjects (LCA, -15.3 +/- 2.3 beats/min; RCA, -6.9 +/- 1.9 beats/min; p less than 0.05 vs. control). This occurred despite significant and comparable decreases in mean arterial pressure in cardiac transplant patients (LCA, -12.7 +/- 2.3 mm Hg; RCA, -11.4 +/- 2.2 mm Hg) and control subjects (LCA, -18.7 +/- 1.7 mm Hg; RCA, -10.7 +/- 1.6 mm Hg). The donor SNR slowed for LCA injection (-5.4 +/- 2.1 beats/min, p less than 0.05) and RCA injection (-3.0 +/- 1.7 beats/min), which, for the LCA, was less than the slowing of control subjects (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
HMG CoA reductase inhibitors lower LDL cholesterol without reducing Lp(a) levels.
Authors: Kostner G M , Gavish D , Leopold B , Bolzano K , Weintraub M S , Breslow J L
Published: June 2011

Lp(a) is a plasma lipoprotein particle consisting of a plasminogenlike protein [apo(a)] disulfide bonded to the apo B moiety of low-density lipoprotein (LDL). Increased plasma levels of Lp(a), either independently or interactively with LDL levels, have been shown to be a risk factor for atherosclerosis. Recently, a new class of lipid-lowering drugs, HMG CoA reductase inhibitors, have been introduced. These drugs act by decreasing liver cholesterol synthesis resulting in up-regulation of LDL receptors, increased clearance of LDL from plasma, and diminution of plasma LDL levels. In this study, we examined the effect of HMG CoA reductase inhibitors on Lp(a) levels in three groups of subjects, five volunteers and two groups of five and 14 patients. In all 24 subjects, mean decreases were observed in total cholesterol (43 +/- 5%), total triglyceride (35 +/- 8%), very low-density lipoprotein (45 +/- 9%), and LDL cholesterol (43 +/- 5%). The mean change in high-density lipoprotein cholesterol was an increase of 7 +/- 8%. Despite the very significant decrease in LDL cholesterol levels (p less than 0.001), Lp(a) levels increased by 33 +/- 12% (p less than 0.005). This was not associated with a measurable change in the chemical composition or size of the Lp(a) particle. This emphatically suggests that Lp(a) particles, despite consisting principally of LDL, are cleared from plasma differently than LDL. The surprising finding of an increase in Lp(a) levels suggests this class of drugs may have a direct effect on Lp(a) synthesis or clearance independent of its effect on LDL receptors.
13N ammonia myocardial imaging at rest and with exercise in normal volunteers. Quantification of absolute myocardial perfusion with dynamic positron emission tomography.
Authors: Krivokapich J , Smith G T , Huang S C , Hoffman E J , Ratib O , Phelps M E , Schelbert H R
Published: June 2011

Positron emission tomography (PET) was applied to the measurement of myocardial perfusion using the perfusion tracer 13N-labeled ammonia. 13N ammonia was delivered intravenously to 13 healthy volunteers both at rest and during supine bicycle exercise. Dynamic PET imaging was obtained in three cross-sectional planes for 10 minutes commencing with each injection. The left ventricle was divided into eight sectors, and a small region of interest was assigned to the left ventricular blood pool to obtain the arterial input function. The net extraction of 13N ammonia was obtained for each sector by dividing the tissue 13N concentration at 10 minutes by the integral of the input function from the time of injection to 10 minutes. With this approach for calculating net extractions, rest and exercise net extractions were not significantly different from each other. To obviate possible overestimation of the true 13N ammonia input function by contamination by 13N-labeled compounds other than 13N ammonia or by spillover from myocardium into blood pool, the net extractions were calculated using only the first 90 seconds of the blood and tissue time-activity curves. This approach for calculating net extractions yielded significant differences between rest and exercise, with an average ratio of exercise to rest of 1.38 +/- 0.34. Nonetheless, the increase was less than predicted from the average 2.7-2.8-fold increase in double product at peak exercise or the 1.7-fold increase in double product at 1 minute after exercise. However, when the first 90 seconds of dynamic data were fit with a two compartment tracer kinetic model, average perfusion rates of 0.75 +/- 0.43 ml/min/g at rest and 1.50 +/- 0.74 ml/min/g with exercise were obtained. This average increase in perfusion of 2.2-fold corresponded to similar average increases in double product. Thus, the noninvasive technique of PET imaging with 13N ammonia shows promise for future applications in determining absolute flows in patients with coronary artery disease.
Seeding of intravascular stents with genetically engineered endothelial cells.
Authors: Dichek D A , Neville R F , Zwiebel J A , Freeman S M , Leon M B , Anderson W F
Published: June 2011

The use of intravascular stents may be limited by both local thrombosis and restenosis due to intimal proliferation. In an effort to provide solutions to these problems, we seeded stents with genetically engineered endothelial cells in vitro. Using retroviral-mediated gene transfer, we inserted the gene for either bacterial beta-galactosidase or human tissue-type plasminogen activator (t-PA) into cultured sheep endothelial cells. The endothelial cells were seeded onto stainless steel stents and grown until the stents were covered. Expression of intracellular beta-galactosidase and high level secretion of t-PA were demonstrated both before and after the transduced cells were seeded onto the stents. Eight stents were expanded by in vitro balloon inflation, with observation of the seeded endothelial layer both prior to and after expansion. Most of the endothelial cells remained on the stents after balloon inflation. We conclude that intravascular stents can be coated with a layer of genetically engineered endothelial cells that can be either specifically labeled or made to secrete high levels of a therapeutic protein. Much of the layer of genetically engineered cells remains after the expansion of the stent in vitro. In vivo implantation of stents coated with genetically engineered endothelial cells may allow 1) introduction of genetically engineered endothelial cells directly into the vascular wall and 2) improvement of stent function through localized delivery of anticoagulant, thrombolytic, or antiproliferative molecules.
Transesophageal low-energy cardioversion in an animal model of life-threatening tachyarrhythmias.
Authors: Cai Y C , Fan S L , Feng D X , Gan S X , Feng J F , Kuang Z S , Li Z F
Published: June 2011

The purpose of this study was to determine the feasibility and efficacy of terminating life-threatening ventricular tachyarrhythmia by low-energy synchronous or asynchronous shocks delivered through a transesophageal catheter that had both an anode and a cathode. Forty-three episodes of ventricular fibrillation or flutter (Vf or VF) were provoked by transesophageal asynchronous random shocks occurring during the vulnerable period of the ventricular cycle in seven dogs and seven pigs that were healthy adults. The 43 episodes of Vf or VF were terminated by the transesophageal technique. The defibrillation energy thresholds were 23.11 +/- 6.28 J (range, 5-30 J). Seven episodes of ventricular tachycardia (VT) with a cycle length of 360 msec or less (330 +/- 27 msec) were provoked by ventricular pacing stimuli during acute myocardial ischemia resulting from delayed resuscitation in two dogs and three pigs. Five of the seven VTs had a duration of 31 seconds or more, and they were all terminated by transesophageal synchronous shocks, the cardioversion thresholds being 1.71 +/- 2.25 J (range, 0.25-5 J). Fourteen episodes of idioventricular tachycardia (IVT) with a cycle length of 400 msec or more (445 +/- 33.5 msec) spontaneously occurred after the use of adrenaline and after defibrillation in four dogs and five pigs. We also succeeded in terminating seven episodes of IVT with a duration of 34 seconds or more by the same means of treating VT, although IVT is not an indication for cardioversion in the clinical setting.(ABSTRACT TRUNCATED AT 250 WORDS)
Comparison of measures of left ventricular contractile performance derived from pressure-volume loops in conscious dogs.
Authors: Little W C , Cheng C P , Mumma M , Igarashi Y , Vinten-Johansen J , Johnston W E
Published: June 2011

Three measures of left ventricular (LV) performance derived from pressure (P)-volume (V) loops have been proposed: the end-systolic P-V (PES-VES) relation, the stroke work-end-diastolic V (SW-VED) relation, and maximum dP/dt-VED (dP/dtmax-VED) relation. We evaluated the variability of repeated determinations, and inotropic and load sensitivity of these relations in conscious dogs. LVV was determined from three orthogonal LV diameters measured by sonomicrometry. Three to six sets of variably loaded P-V loops were generated by transient caval occlusions before and again after increasing inotropic state by infusing dobutamine (6 +/- 1 microgram/kg/min, mean +/- SD) and after increasing PES by 49 +/- 17 mm Hg with phenylephrine following autonomic blockade. The slope (MSW) of the SW-VED relation was the least variable at constant inotropic state (coefficient of variation, 4 +/- 3%) compared with the slope (EES) of the PES-VES relation (8 +/- 3%) or the slope (dE/dtmax) of the dP/dtmax-VED relation (11 +/- 6%, p less than 0.05). The extrapolated volume-axis intercept of the SW-VED relation was much less variable than the intercepts of the PES-VES or dP/dtmax-VED relations. MSW, EES, and dE/dtmax all increased (p less than 0.05) in response to dobutamine. The extrapolated volume-axis intercepts of the PES-VES and dP/dtmax-VED relations increased with dobutamine, whereas the volume intercept of the SW-VED relation was unchanged. MSW had the smallest increase in response to dobutamine (124 +/- 22% of control) compared to EES (178 +/- 67% of control) and dE/dtmax (211 +/- 68% of control, p less than 0.05). The position of the PES-VES relation, quantified as the VES at PES = 100 (V100), showed less variability (2 +/- 1%) than the slope of the PES-VES relation (8 +/- 3%, p less than 0.05). V100 decreased from 30.8 +/- 17.4 to 26.7 +/- 13.7 ml during dobutamine (p less than 0.05). After phenylephrine, EES, MSW, and dE/dtmax decreased by less than 10% (p = NS). The PES-VES relation shifted to the left with this increased afterload and V100 decreased by 3.2 +/- 1.5 ml (p less than 0.05), whereas the position of the SW-VED and dp/dtmax-VED relations were relatively unchanged.(ABSTRACT TRUNCATED AT 400 WORDS)
Effects of graded reductions in coronary perfusion pressure on the diastolic pressure-segment length relation and the rate of isovolumic relaxation in the resting conscious dog.
Authors: Farhi E R , Canty J M , Klocke F J
Published: June 2011

To assess the relations between coronary perfusion pressure, blood flow, and the diastolic pressure-segment length relation in the conscious animal, circumflex pressure was incrementally decreased in 10 resting, chronically instrumented dogs by a hydraulic occluding cuff while monitoring left ventricular pressure and regional segment length (with piezoelectric crystals) in the circumflex and left anterior descending territories. In five dogs, regional blood flow was measured by microsphere injections at selected circumflex pressures. The diastolic portion of the pressure-segment length curve was unchanged when decrements in circumflex pressure were within the autoregulatory range, that is, unassociated with changes in blood flow or systolic function. Further decrements in circumflex pressure, which decreased blood flow and regional segment shortening (both p less than 0.05), caused a progressive downward and rightward shift of the pressure-segment length curve (p less than 0.05). The rate of relaxation, as measured by tau (the time constant of pressure decay during isovolumic relaxation, which is calculated assuming either a fixed or a variable asymptote) and peak negative dP/dt, decreased slightly during reductions in circumflex pressure within the autoregulatory range and greatly at lower pressure (all p less than 0.05). Thus, in the conscious animal, reductions in coronary perfusion pressure within the autoregulatory range do not affect the diastolic pressure-segment length curve but cause modest decreases in the rate of isovolumic relaxation. Further reductions in coronary perfusion pressure, below the limits of blood flow autoregulation, cause an increased extent of relaxation with a marked downward shift of the diastolic pressure-segment length curve as well as a large decrease in the rate of relaxation.
Cellular abnormalities in chronically denervated myocardium. Implications for the transplanted heart.
Authors: Drake-Holland A J , Noble M I
Published: June 2011

Heart transplantation involves chronic effects due to denervation, rejection, and treatment of rejection. The chronically denervated dog heart provides a model for the effects of denervation alone. These hearts have been shown to contain intrinsic neurons with VIP and NPY as possible neurotransmitters. Myocardial tissue noradrenaline concentration falls to very low levels after degeneration of postganglionic sympathetic neurons, but dopamine remains in near-normal concentration and is probably synthesized extraneuronally. ANP is present and released normally; however, the natriuretic response to atrial distension is blunted, suggesting that this response is mainly due to a reflex mechanism. Chronically denervated myocardial tissue exhibits increased oxygen consumption in vitro and increased Na-K, ATPase activity but has normal tissue levels of ATP and creatine phosphate. Glucose oxidation is inhibited in vivo, associated with increased levels of fructose-6-phosphate but normal glucose-6-phosphate, suggesting inhibition of phosphofructokinase activity. However, the enzyme protein concentration of phosphofructokinase, as judged by maximal in vitro activity, is normal. Maximal in vitro activities of succinate dehydrogenase, cytochrome oxidase, monoamine oxidase, calcium-dependent ATPase, and glyceraldehyde-3-dehydrogenase are also normal. From these findings, we would predict that patients with transplanted hearts are likely to show myocardial metabolic inefficiency.
Recurrent ischemia more than 1 year after successful percutaneous transluminal coronary angioplasty. An analysis of the extent and anatomic pattern of coronary disease.
Authors: Bottner R K , Green C E , Ewels C J , Recientes E , Patrissi G A , Kent K M
Published: June 2011

Of 1,181 consecutive patients who underwent successful percutaneous transluminal coronary angioplasty (PTCA) as an initial revascularization procedure and who had at least 1 year of asymptomatic follow-up, 66 (6%) underwent repeat angiography because of recurrent symptoms or evidence of exercise-induced ischemia. Patients who had revascularization procedures within 1 year of PTCA were not included in the analysis. Mean time to recurrent ischemia was 30.8 +/- 17.4 months (range 12-89 months). At follow-up, 47 patients had angina, 13 had atypical chest pain, two had acute myocardial infarction, and four had positive exercise tests without symptoms. No patient showed spontaneous regression in the extent of coronary artery disease (CAD). As compared with the extent of CAD immediately after PTCA, the extent of CAD at follow-up did not change in 26 patients (39%); it increased by one vessel in 30 (45%), by two vessels in seven (11%), and by three vessels in three (5%). The pattern of CAD seen at follow-up compared with that seen after PTCA was as follows: 18 patients (27%), no change; seven (11%), restenosis only; 30 (45%), progression of CAD at other sites only; and 11 (17%), a combination of restenosis and progression of CAD at other sites. The time to recurrence of ischemia was significantly different between those with restenosis only versus those with progression only (20.1 +/- 9.2 vs. 38.3 +/- 18.5 months) (p less than 0.009). Progression of CAD was equally distributed between dilated and nondilated vessels; however, when progression occurred in the PTCA vessel, it was significantly more likely to be distal to the PTCA site (p less than 0.008).
Noninvasive detection of skeletal muscle underperfusion with near-infrared spectroscopy in patients with heart failure.
Authors: Wilson J R , Mancini D M , McCully K , Ferraro N , Lanoce V , Chance B
Published: June 2011

The present study was undertaken to determine whether near-infrared spectroscopy can be used to noninvasively assess skeletal muscle oxygenation in patients with heart failure. The difference between light absorption at 760 and 800 nm was used to assess hemoglobin-myoglobin oxygenation. Initial studies conducted in isolated canine gracilis muscle demonstrated that 760-800-nm absorption correlated closely (r = -0.97 +/- 0.01) with venous hemoglobin O2 saturation when the muscle was stimulated to contract at 0.25-5.0 Hz. In normal subjects (n = 6) and patients with heart failure (n = 8), 760-800-nm absorption changes from the vastus lateralis muscle were monitored at rest, during progressive maximal bicycle exercise, and during thigh cuff inflation to suprasystolic pressure, an intervention designed to assess minimal hemoglobin-myoglobin oxygenation. Absorption changes were expressed relative to the full physiologic range noted from rest to thigh cuff inflation. During exercise, normal subjects exhibited an initial increase in hemoglobin-myoglobin oxygenation followed by a progressive decrease in oxygenation to 27 +/- 13% of the physiologic range at the peak exercise workload of 140 +/- 9 W. In contrast, patients exhibited an initial decrease in hemoglobin-myoglobin oxygenation with the first workload, followed by a progressive further decrease to 26 +/- 13% of the physiologic range at a peak exercise workload of 60 +/- 8 W, less than half the peak workload noted in the normal subjects. At all exercise loads, hemoglobin-myoglobin oxygenation was significantly less in the patients than in the normal subjects. These data suggest that near-infrared spectroscopy can detect impaired skeletal muscle O2 delivery in patients with heart failure. This technique could provide a valuable method of assessing muscle O2 delivery in patients, particularly before and after therapeutic interventions.
Metabolic protection by verapamil during graded coronary flow reduction independent of effect on baseline systolic function. Separation of mechanical and ionic markers of ischemia.
Authors: Jenkins M G , Johnson T A , Engle C , Gettes L S
Published: June 2011

Pretreatment with the calcium channel-blocking agent verapamil lowers the coronary flow associated with the first rise in myocardial extracellular potassium [( K+]e). The mechanisms underlying this effect are unclear. It is not known whether this effect is a manifestation of verapamil-induced reduction in baseline cardiac work before the reduction in coronary flow, is dependent on a selective depression of contractility within the low-flow region, or is independent of an effect on myocardial work. This study was performed to determine the relations between changes in regional contractility and [K+]e before and after verapamil (0.2 mg/kg followed by 6.5 micrograms/kg/min) when left anterior descending (LAD) coronary flow is progressively reduced and when verapamil-induced alterations in baseline myocardial work are prevented by atrial pacing and by dobutamine (4.3 +/- 2.2 micrograms/kg/min) to maintain systemic arterial blood pressure and contractility. Before verapamil-dobutamine, myocardial [K+]e rose and regional contractility fell when LAD coronary flow was reduced to 87.7 +/- 9.6% and 83.4 +/- 7.4%, respectively, of the unrestricted control value (p = NS). After verapamil-dobutamine, the threshold flow for rise in [K+]e decreased to 56.4 +/- 13.5% of the unrestricted control flow (p = 0.003), but the threshold flow for regional contractility fall was unchanged (84.8 +/- 11.3%). Our results indicate that the protective effect of verapamil on preventing ischemia-induced [K+]e release is not dependent on a reduction in baseline myocardial work. In this setting, calcium channel blockade by verapamil results in a dissociation between the ionic and mechanical events that occur when coronary flow is reduced.
Reflex responses to myocardial ischemia and reperfusion. Role of prostaglandins.
Authors: Thames M D , Minisi A J
Published: June 2011

Powerful vasodepressor and cardioinhibitory reflexes are activated in humans during inferior wall myocardial ischemia or infarction and during restoration of flow to the ischemic region. Experiments in dogs have demonstrated that these responses are due to stimulation of afferent vagal fibers that are located mainly in the inferior wall of the heart. Prostaglandins are released during myocardial ischemia and possibly during reperfusion. Prostaglandins stimulate chemosensitive but not mechanosensitive endings in the ventricles. Our studies determined whether blockade of prostaglandin synthesis with indomethacin or sodium meclofenamate decreased the reflex inhibitory responses to coronary occlusion and reperfusion. Experiments were done in alpha-chloralose-anesthetized dogs after sinoaortic baroreceptor denervation. Occlusion of the circumflex coronary artery for 5 minutes resulted in decreases in arterial pressure and in renal sympathetic nerve activity. During the first 5 minutes after release of the occlusion, renal nerve activity remained inhibited. After treatment with indomethacin (n = 6, 5 mg/kg i.v.) or sodium meclofenamate (n = 3, 4 mg/kg i.v.), coronary occlusion resulted in significantly less inhibition of renal nerve activity. Renal nerve activity returned to control during the first minute of reperfusion. In six additional experiments the responses to coronary occlusion and reperfusion were not altered by treatment with vehicle. Our data suggest that prostaglandins serve as the major stimulus to ventricular sensory endings during myocardial ischemia and reperfusion. Our data further suggest that reflex inhibitory responses during ischemia and reperfusion are due mainly to stimulation of chemosensitive endings.
Impact of Fontan operation on left ventricular size and contractility in tricuspid atresia.
Authors: Gewillig M H , Lundström U R , Deanfield J E , Bull C , Franklin R C , Graham T P , Wyse R K
Published: June 2011

Left ventricular dimensions and contractility were determined by echocardiography in 33 patients with tricuspid atresia in 1985 and again in 1988. Eight patients remained palliated throughout the 3-year period; neither the left ventricular end-diastolic diameter (153 +/- 15% of normal vs. 157 +/- 19%, p = NS) nor a load-independent index of contractility (rate-corrected velocity of shortening [VCFc]/end-systolic meridional stress [ESSM]) changed. Eleven patients underwent a Fontan operation during the study and were reevaluated at least 6 months after surgery; left ventricular dimension decreased (130 +/- 15% vs. 114 +/- 19%, p less than 0.001), and the contractility index VCFc/ESSM improved (p less than 0.05). Fourteen patients had undergone a Fontan operation 0.9-9.5 years (mean, 4.2 years) before initial examination in 1985. Over the 3-year period, left ventricular dimensions did not change (121 +/- 17% vs. 118 +/- 11%, p = NS), but the contractility index showed significant improvement (p less than 0.01). Eight additional patients were studied just before and after a Fontan operation to examine the early effects of surgery. Left ventricular dimensions decreased from 130 +/- 14% to 100 +/- 13% by 10 days p less than 0.001) with no further change at 2 months. An inappropriate degree of ventricular hypertrophy was observed in only the early postoperative period. Successful Fontan repair results in rapid reduction of left ventricular size, followed by regression of hypertrophy to a normal mass-to-volume ratio. Operating at more favorable dimensions and loading conditions results in an early increase in left ventricular contractility, which further improves in the medium term follow-up.
Sudden death after repair of double-outlet right ventricle.
Authors: Shen W K , Holmes D R , Porter C J , McGoon D C , Ilstrup D M
Published: June 2011

The outlook for patients with double-outlet right ventricle has improved since the development of corrective operations. Late arrhythmic deaths after successful procedures have been reported; however, the magnitude remains unknown. This study was undertaken to identify the magnitude of late sudden death and the significant factors associated with it. From 1965 through 1985, 118 patients underwent corrective operation for double-outlet right ventricle; of these, 23 died in the hospital and six were lost to follow-up. The 89 remaining patients (52 male and 37 female) made up the study population. Their mean age (+/- SD) was 10.3 +/- 7.8 years at the time of repair. The mean duration of follow-up was 82 months. Of the 22 late deaths, 16 (73%) were sudden. Eight (50%) of the sudden deaths occurred within 1 year of operation. Cox proportional hazards multivariate analysis revealed the following significant risk factors for late sudden death: older age at the time of operation, perioperative or postoperative ventricular tachyarrhythmias, and third-degree atrioventricular block. Factors not associated with late sudden death included year of operation, sex, type and number of associated cardiac anomalies, preoperative functional class, previous palliative procedures, surgical technique, perioperative or postoperative single premature ventricular contractions, and postoperative left or right bundle branch block with or without fascicular block. We conclude that the incidence of late sudden death after successful surgical repair of double-outlet right ventricle is very high. Complete corrective operation at an early age and aggressive diagnosis and treatment of arrhythmias and conduction defects after operation are warranted.
Fluorescence-guided laser-assisted balloon angioplasty in patients with femoropopliteal occlusions.
Authors: Leon M B , Almagor Y , Bartorelli A L , Prevosti L G , Teirstein P S , Chang R , Miller D L , Smith P D , Bonner R F
Published: June 2011

In 12 patients (aged 64 +/- 10 years) with femoropopliteal occlusions (1-27 cm; average, 8.4 cm length) that could not be recanalized by standard guidewire-balloon angioplasty techniques, percutaneous laser-assisted balloon angioplasty was performed by use of a new fluorescence-guided dual-laser system. Plaque detection by 325-nm laser-excited fluorescence spectroscopy provided real-time feedback control to a 480-nm pulsed dye laser (2-microseconds pulses) for atheroma ablation. By means of a common 200-microns optical fiber, after diagnostic fluorescence sensing, computer algorithms directed a fire or no-fire signal (5 Hz) to the treatment laser for selective plaque removal. Laser recanalization (15-50 mJ/pulse) was successful in 10 of 12 patients; this procedure was followed by definitive balloon angioplasty in seven of 12 patients with increased ankle/arm indexes (from 0.60 +/- 0.12 at baseline to 0.84 +/- 0.11 after treatment, p = 0.0043). In laser and balloon angioplasty failures, all femoropopliteal occlusions were heavily calcified, and there were two mechanical guidewire perforations without clinical sequelae. Ablation of calcified lesions required higher pulse energies and greater total energy per centimeter of recanalized tissue (1,837 +/- 1,251 mJ/cm vs. 90 +/- 39 mJ/cm, p = 0.0036). Fluorescence spectroscopy (n = 219 sites) was helpful in flush occlusions and correctly identified plaque, underlying media, and thrombus by changes in fluorescence intensity, shape, and peak position. Thus, when fluorescence-guided laser angioplasty was used in a subgroup of patients refractory to standard angioplasty techniques, primary recanalization and subsequent balloon angioplasty of femoropopliteal occlusions was successful in 83% and 58% of the patients, respectively. Importantly, treatment of heavily calcified lesions accounted for all of the failures and will require modified delivery systems to create larger primary channels and to increase catheter-tip control, which should improve clinical results in the future.
The complement system in ischemic heart disease.
Authors: Yasuda M , Takeuchi K , Hiruma M , Iida H , Tahara A , Itagane H , Toda I , Akioka K , Teragaki M , Oku H
Published: June 2011

The mechanisms by which tissue injury after acute myocardial infarction (AMI) occurs has not been fully elucidated. Recent evidence in experimental models has suggested involvement of the complement system in microvascular and macrovascular injury subsequent to AMI. With respect to angina pectoris, whether or not the complement system is activated is not clear. The present study assessed the role of complement as a mediator of myocardial inflammation by quantifying products of complement activation, including C3d, C4d, Bb, and SC5b-9 complexes, in 31 patients with AMI, 17 patients with unstable angina pectoris, 19 patients with stable angina pectoris, and 20 normal volunteers. The plasma C3d levels increased in patients with AMI and in those with unstable angina pectoris (p less than 0.01). The plasma levels of C4d, Bb, and SC5b-9 increased only in patients with AMI (p less than 0.01). The plasma SC5b-9 level was related to peak creatine phosphokinase (r = 0.71) and inversely related to the ejection fraction (r = -0.71). The plasma SC5b-9 level of patients with congestive heart failure was higher than that of patients without congestive heart failure in AMI. These results show that activation of complement system occurs after AMI and show an association of myocardial damage with complement activation. With respect to angina pectoris, the complement system is mildly activated in patients with unstable angina pectoris; however, the cardiac function of patients with unstable angina pectoris is not damaged. The complement system of patients with stable angina pectoris is not activated.
Calcium attenuates epinephrine's beta-adrenergic effects in postoperative heart surgery patients.
Authors: Zaloga G P , Strickland R A , Butterworth J F , Mark L J , Mills S A , Lake C R
Published: June 2011

Epinephrine and calcium possess both cardiac inotropic and vasopressor activity. In addition, epinephrine's cardiovascular effects are mediated via increases in intracellular calcium. As a result, many clinicians administer the two agents together in an attempt to augment their effects. Although this approach seems rational, it has never been proven effective. We evaluated the cardiovascular and hyperglycemic actions of epinephrine (10 and 30 ng/kg/min), with and without calcium chloride administration (10 mg/kg bolus followed by 2 mg/kg/hr infusion), in a prospective, randomized, blinded, crossover designed study. Twelve adult patients were studied 1 day after aortocoronary bypass surgery. Calcium chloride raised ionized calcium levels from 1.06 +/- 0.03 (mean +/- SEM) to 1.44 +/- 0.05 mM (p less than 0.05). Calcium raised mean arterial pressure from 85 +/- 1 to 94 +/- 2 mm Hg (p less than 0.05) but had no significant effect on cardiac index. Epinephrine alone at 10 and 30 ng/kg/min significantly raised cardiac index from 2.7 +/- 0.2 to 3.0 +/- 0.2 (p less than 0.05) and 3.6 +/- 0.3 (p less than 0.05) l/min/m2. After calcium, epinephrine failed to significantly increase cardiac index. Epinephrine at 30 ng/kg/min significantly increased mean arterial pressure from 87 +/- 1 to 95 +/- 2 mm Hg (p less than 0.05). After calcium, epinephrine had no significant effect on blood pressure. In addition, epinephrine's hyperglycemic effect was blunted by calcium. Plasma epinephrine levels were similar during control and calcium infusions. We conclude that calcium blunts epinephrine's beta-adrenergic actions in postoperative cardiac surgery patients.