Angina and persistent exercise thallium defects: independent risk factors in elective vascular surgery.

OBJECTIVES: In this study, we assessed the utility of exercise thallium-201 scintigraphy and other clinical factors in predicting perioperative cardiac complications in patients undergoing elective vascular surgery. BACKGROUND: The risk of cardiac complications among such patients is very high. METHODS: The study group comprised 116 men (mean age 67 years). Fifty patients (43%) had a history of coronary artery disease, including angina pectoris in 26 (22%), myocardial infarction in 32 (28%) and coronary artery bypass surgery in 19 (16%). RESULTS: There were a total of 22 perioperative myocardial infarctions (18.9%), including 2 cardiac deaths (1.7%). A significantly greater proportion (p < 0.05) of patients with than without perioperative complications had a history of coronary artery disease (77% vs. 35%), angina (59% vs. 14%), prior myocardial infarction (50% vs. 22%), abnormal electrocardiogram (68% vs. 40%) and abnormal exercise thallium test (75% vs. 47%). The patient group with complications also had a significantly lower mean rest ejection fraction (45 +/- 3% vs. 55 +/- 2%, p < 0.005). Independent predictors of complication, as determined by straight logistic regression, were angina and fixed thallium defects after exercise. CONCLUSIONS: Our data indicate that angina and the presence of fixed thallium defects after exercise are independent predictors of cardiac risk in patients undergoing elective vascular surgery. These findings are compatible with other studies showing that nonredistribution on standard 3- to 4-h delayed studies cannot exclude viable myocardium at risk.

Effects of dobutamine stimulation on regional myocardial glucose uptake poststunning as measured by positron emission tomography.

OBJECTIVES: The aim was to determine whether dobutamine stimulation of energy expenditure within the postischaemic myocardium would affect regional differences in glucose uptake as measured by positron emission tomography (PET). METHODS: The metabolic rate of glucose uptake within the myocardium can be assessed with the glucose analog 18F-fluorodeoxyglucose (FDG). Stunning was induced in 14 anaesthetised pigs by partially occluding the left anterior descending coronary artery (LAD) for 20 min (> 80% flow reduction). The metabolic rate of glucose uptake was determined 2 h after reperfusion in the LAD and non-LAD regions in two groups: without (group 1; n = 7) and during (group 2; n = 7) a constant intravenous infusion of dobutamine (4 micrograms.kg-1.min-1). RESULTS: In all pigs, stunning reduced systolic shortening from 16(SD 4)% to 5(5)% (p < 0.05) and slightly lowered myocardial oxygen consumption, from 3.18(1.21) to 2.67(0.93) mumol.min-1.g-1 (p = 0.08). In the postischaemic LAD region of group 1, the metabolic rate of glucose uptake was significantly lower than the non-LAD region (0.11(0.08) and 0.43(0.33) mumol.min-1.g-1 respectively). In group 2, dobutamine induced a sustained increase in both fractional shortening (7(4)% to 16(5)%; p < 0.05) and oxygen consumption (2.34(0.94) to 4.53(1.52) mumol.min-1.g-1; p < 0.05) within the postischaemic LAD region. Despite recruitment of function and oxygen consumption in group 2, the metabolic rate of glucose uptake was similar to that of group 1 (0.11(0.09) and 0.40(0.28) mumol.min-1.g-1 in LAD and remote regions respectively). CONCLUSIONS: In this pig model of stunning, uptake of FDG was lower in stunned compared with remote myocardium and was independent of postischaemic changes in oxygen consumption and wall thinning. This supports the contention that after stunning, non-glucose substrates play an important part in maintaining energy expenditure during catecholamine stimulation.

Relation of lactate production to postischaemic reduction in function and myocardial oxygen consumption after partial coronary occlusion in swine.

Postischaemic myocardial dysfunction (stunning) induced by partial occlusion of the left anterior descending coronary artery and its relation to lactate production during reperfusion were studied in nine swine. A 40% reduction in regional left ventricular wall thickening, as measured by ultrasonic crystals, was prospectively defined as stunning. A perfusion pressure of 20 mmHg was maintained with a hydraulic occluder for each ischaemic period and was monitored by a distal arterial catheter. To achieve a 40% reduction in function, four animals required three ischaemic periods (mean ischaemic flow reduction 73%), four two (86% flow reduction), and one one (93% flow reduction). At 25 min of reperfusion transmural flow was slightly reduced from 0.67 ml.g-1.min-1 at control to 0.58 ml.g-1.min-1 (p less than 0.05), whereas regional flow endocardial to epicardial flow ratio was unchanged. At 60 min reperfusion, percentage systolic wall thickening was reduced to 25% from a control of 39% (p less than 0.01) and parallel reductions in regional myocardial oxygen consumption from 4.3 ml.min-1 to 2.7 ml.min-1 occurred (p less than 0.01). Lactate extraction was depressed at 15 min reperfusion (-4.0% compared with control +18.0% (p less than 0.05)) but returned to control values by 30 min. It is concluded that postischaemic myocardial dysfunction (stunning) can be induced by partial coronary occlusions and that the extent of dysfunction depends on the degree of flow reduction. The reductions in myocardial oxygen consumption parallel those of wall thickening during reperfusion after stunning. Finally, lactate production occurs during early reperfusion but does not persist with the postischaemic reductions in function and myocardial oxygen consumption.

Importance of vasomotor tone to myocardial function and regional metabolism during constant flow ischaemia in swine.

STUDY OBJECTIVE: The aim was to test the hypothesis that the release of vascular tone with adenosine during constant flow ischaemia alters both transmural function and regional metabolism in a detrimental way. DESIGN: In one group of anaesthetised swine, the effects of graded reductions of flow on segmental left ventricular function, myocardial oxygen consumption (MVO2), and lactate production in the distribution of the left anterior descending coronary artery (LAD) were determined. In a second group, a model of constant flow ischaemia was induced to test how altering vascular tone with adenosine changed the relationship of flow, function, and metabolism. EXPERIMENTAL MATERIAL: The experiments were performed in 20 open chest, anaesthetised swine. Protocol A consisted of 11 animals and protocol B of nine animals. MEASUREMENTS AND MAIN RESULTS: In protocol A, during graded ischaemia, reductions in flow, % systolic wall thickening (WTh), normalised MVO2 and % lactate extraction (%LE) correlated well with reductions in coronary perfusion pressure when fitted with 3rd order polynominal curves (r = 0.78, 0.87, 0.85 and 0.81 respectively; p less than 0.00001). In protocol B, during constant flow ischaemia, at control, % WTh was 33 (SD 11)%, mean coronary artery pressure was 72(10) mm Hg, mean LAD transmural flow was 0.99(0.43) ml.min-1.g-1, and % LE was +14(9)%. With inflation of a hydraulic occluder on the LAD, perfusion pressure was lowered to 38(5) mm Hg and transmural flow dropped to 0.76(0.31) ml.min-1.g-1 (intact vasomotion). During an infusion of intracoronary adenosine with flow held constant (absent vasomotion), %WTh was further reduced from 27(9) to 13(10) (p less than 0.001), and %LE from -18(42) to -70(61) (p less than 0.05). MVO2 with and without vasomotion did not differ significantly at 3.14(0.75) and 3.18(0.86) ml.min-1.g-1 respectively. CONCLUSION: In swine coronary circulation, reductions in regional function, MVO2 and lactate production correlate well with reductions in flow and perfusion pressure during ischaemia with vasomotor tone intact. The effect of adenosine on vascular tone during constant flow ischaemia caused dramatic reductions in function and lactate extraction without altering MVO2. This emphasises the important role of vascular tone in protecting both transmural function and regional metabolism during moderate ischaemia.

Endothelium dependent vasodilatation following brief ischaemia and reperfusion in anaesthetised swine.

STUDY OBJECTIVE: The aim as to compare the responses of intracoronary infusions of ATP, an endothelium dependent vasodilator, with adenosine following brief ischaemia (10 min) and reperfusion in a model of myocardial stunning. DESIGN: In group 1 (n = 6), coronary blood flow and endocardial (endo) and epicardial (epi) percent segment length shortening were measured in the distribution of the left anterior descending coronary artery before and during maximal intracoronary infusions of either adenosine or ATP (20 micrograms.kg-1.min-1). Measurements were obtained before and after myocardial stunning both at control heart rate and during atrial pacing (150 beats.min-1). In group 2 (n = 6), myocardial blood flows by microspheres and arterial-venous lactate and oxygen differences were determined following the same ischaemia-reperfusion protocol to characterise transmural changes in blood flow and metabolism in this model of stunning. EXPERIMENTAL MATERIAL: The experiments were done on 12 anaesthetised swine, weight 25-39 kg. MEASUREMENTS AND MAIN RESULTS: In group 1, baseline endo and epi segment length shortening were 16(SD 3)% and 14(6)% and following reperfusion were reduced to 10(4)% and 8(6)% respectively (p less than 0.05). Prior to stunning, minimal coronary resistances during adenosine and ATP were 0.81(0.40) and 0.76(0.25) mm Hg.min.ml-1 respectively and following reperfusion were 0.86(0.31) (NS) and 0.85(0.23) (NS) mm Hg.min.ml-1 respectively. Infusion of either vasodilator enhanced function by 30% following reperfusion whereas no such effect was observed prior to ischaemia. In group 2, no maldistribution of blood flow was observed following the same ischaemia-reperfusion protocol to account for this vasodilator enhancement in function. Percent lactate extraction values were 29(11)% and 25(14)% at preischaemic control and paced heart rates respectively, and following reperfusion were lowered to 0(12)% without pacing (p less than 0.05) and -1(34)% during pacing (p less than 0.05). CONCLUSIONS: Brief ischaemia and reperfusion in swine induces myocardial stunning without altering the vasodilator responses of either ATP, an endothelium dependent vasodilator, or adenosine. Recruitment in postischaemic segment length shortening was observed during infusions of both vasodilators at a time when maldistribution of flow was not observed. Possible mechanisms include either enhanced washout of lactate from the reperfused myocardium or greater utilisation of substrates during higher blood flows.

Dobutamine restores the reduced efficiency of energy transfer from total mechanical work to external mechanical work in stunned porcine myocardium.

OBJECTIVE: In order to determine whether the relatively high oxygen consumption of stunned myocardium is related to decreased mechanical efficiency, myocardial oxygen consumption (MVO2) and its major determinants were studied in 10 open chest anaesthetised pigs. METHODS: According to the time varying elastance concept, MVO2 is determined by contractility (Emax) and total mechanical work (PLA), which is the sum of the external work (EW) and potential energy (PE). Mechanical efficiency (EW/MVO2) equals the product of EW/PLA (= efficiency of energy transfer or EET) and PLA/MVO2. Emax is the slope of the end systolic pressure-segment length relationship, determined by gradually clamping the aorta. PLA is the area enclosed by the end systolic pressure-segment length relationship and the pressure-segment length trajectory. EW is the area of the pressure-segment length loop. Systemic haemodynamics, regional segment shortening, and MVO2 were determined at baseline, during stunning (two sequences of 10 min occlusion and 30 min of reperfusion), after a subsequent 50 beats.min-1 increase in heart rate by atrial pacing and additional infusion of 2 micrograms.kg-1.min-1 dobutamine. RESULTS: Stunning decreased segment shortening from 18.2(SEM 1.9)% to 10.2(1.5)%, MVO2 from 4.16(0.27) x 10(-2) to 2.84(0.25) x 10(-2) mumol.beat-1.g-1, and Emax from 47(9) to 23(3) mm Hg.mm-1 (all p < 0.05). PLA decreased by 13(4)%, as EW decreased by 42(6)%, and PE tended to increase. Although EET decreased from 0.58(0.04) to 0.40(0.03) (p < 0.05), there was no decrease in the mechanical efficiency, as an increase in PE caused an increase in PLA/MVO2 which compensated for the decrease in EET. Dobutamine infusion increased Emax and EW per beat to 120(23)% and 67(8)% of baseline, respectively, while MVO2 [4.12(0.53) mumol.beat-1.g-1] and EET [0.57(0.04)] returned to baseline. CONCLUSIONS: In stunned myocardium, mechanical efficiency is not decreased despite a decrease in EET. The increase in EET after dobutamine may explain the lack of the excessive increase in MVO2.

Increased activity of the sarcoplasmic reticular calcium pump in porcine stunned myocardium.

OBJECTIVE: The aim was to determine whether changes in sarcoplasmic reticular Ca2+ transport activity and the degree of phosphorylation of phospholamban of "stunned" myocardium are involved in the reversible depression of contractile function. METHODS: In anaesthetised open chest swine, stunning was induced by subjecting the myocardium perfused by the left anterior descending coronary artery to two cycles of 10 min of occlusion and 30 min of reperfusion. Before and after stunning, systemic haemodynamic variables and regional myocardial function and perfusion were determined, while biopsies were taken for determination of the content of high energy phosphate compounds. Sarcoplasmic reticular function (ATP dependent Ca2+ transport and phosphorylation of phospholamban) of the stunned and control myocardium was determined at the end of the stunning protocol. RESULTS: In the stunned myocardium the segment length shortening decreased from 17.4(SD 4.0)% to 3.5(4.4)%, while perfusion was 38% less than at baseline. ATP and total adenine nucleotide levels of the stunned myocardium were about 35% lower than in the control myocardium, but the energy charge was normal as creatine phosphate levels had increased by 66% over the content determined at baseline. Ca2+ uptake by the sarcoplasmic reticulum isolated from the stunned region was 17% (p < 0.05) higher than Ca2+ uptake from the control region [1240(303) and 1450(280) nmol.min-1.mg-1 protein, respectively]. In the presence of exogenous cyclic AMP dependent protein kinase the amount of 32P incorporated into phospholamban was similar for both myocardial regions. CONCLUSIONS: In this model of stunned porcine myocardium, the phosphorylation state of phospholamban was unchanged, but Ca2+ uptake by the sarcoplasmic reticulum was slightly increased. The results indicate that a change in active Ca2+ transport by the sarcoplasmic reticulum is most likely not to be the principal cause of contractile dysfunction of stunned myocardium.

Enhanced gene expression of calcium regulatory proteins in stunned porcine myocardium.

OBJECTIVE: Increasing evidence points to a molecular disturbance of Ca2+ homeostasis in stunned myocardium. The aim of this study was therefore to investigate the expression of mRNAs for Ca2+ binding proteins related to the sarcoplasmic reticulum in a porcine model of myocardial stunning. METHODS: In 22 anaesthetised pigs, stunning was achieved by one or two cycles of 10 min left anterior descending coronary artery occlusion and reperfusion. Hearts were excised at various timepoints of the protocol. Total RNA was extracted from stunned (experimental) as well as normally perfused (control) myocardium. RESULTS: Northern blot analysis using radioactive cDNA probes revealed that the Ca(2+)-ATPase mRNA levels increased 1.6-fold compared to the control value at 90 min of the second reperfusion. The steady state level of phospholamban mRNA rose 2.5-fold at 180 min of reperfusion. A 2.3-fold increase in calsequestrin mRNAs was observed after 90 min of the second reperfusion. The calmodulin and alpha, beta myosin heavy chain mRNA levels were unchanged. A glyceraldehyde-3-phosphate dehydrogenase cDNA probe served as a reference system. Nuclear run-on assays showed increased transcription for Ca(2+)-ATPase and calsequestrin at 90 min of reperfusion, supporting the view that increased mRNA levels seen with northern hybridisation were due to increased transcription of the respective gene. CONCLUSIONS: The results suggest specific repair mechanisms of stunned myocardium and point to the involvement of calcium regulatory proteins related to the sarcoplasmic reticulum in the pathogenesis of myocardial stunning.

Temporal changes in function and regional glucose uptake within stunned porcine myocardium.

UNLABELLED: This study compared the effects of porcine myocardial stunning on the uptake of [18F]-fluorodeoxyglucose (FDG) at 24 hr and 7 days after reperfusion. Prior studies in animals subjected to severe myocardial ischemia have shown a sustained increase in FDG uptake relative to perfusion (FDG/MBF). The time course of recovery of FDG/MBF relative to function poststunning, however, has not been well characterized. METHODS: Stunning was induced in eight swine by partially occluding the LAD artery for 20 min. At 1 and 7 days postreperfusion, function was assessed by two-dimensional echocardiography and PET studies were obtained with FDG and either 15O-water or 13N-ammonia. Blood flow by microspheres was determined at baseline, during ischemia and after stunning. Myocardial uptake of FDG relative to blood flow on matching images (FDG/MBF) was calculated for all ROIs and expressed as a ratio of LAD to non-LAD areas. RESULTS: After stunning, left ventricular ejection fraction (LVEF) increased from 42% +/- 10% on Day 1 to 52% +/- 6% on Day 7 (p < 0.05). At Day 1, myocardial blood flow was 0.60 +/- 0.10 ml/min/g in LAD and 0.67 +/- 0.16 in non-LAD regions and neither differed at Day 7. The magnitude of FDG/MBF in the LAD region when normalized to the non-LAD region was 1.29 +/- 0.16 on Day 1 and 1.09 +/- 0.08 on Day 7 (p < 0.05) and was inversely proportional to global measures of LVEF (r2 = 0.61; p < 0.005). CONCLUSION: The severity of postischemic LV dysfunction at 1 and 7 days after stunning correlates with the degree of enhanced regional glucose uptake as estimated by PET. Both normalize within 7 days, suggesting that metabolic and functional abnormalities within completely reperfused myocardium recover in parallel.

Myocardial blood flow and FDG retention in acutely stunned porcine myocardium.

UNLABELLED: This study assesses regional differences in myocardial blood flow and 18F-fluorodeoxyglucose (FDG) retention in acutely stunned porcine myocardium. METHODS: Two groups of swine were used for these studies. In Group 1, 15 animals underwent stunning induced by 20 min of myocardial ischemia followed by reperfusion. Regional function was measured with ultrasonic crystals and myocardial blood flows were quantitated with radiolabeled microspheres. Within 2 hr postischemia, myocardial blood flow images were obtained with 15O-water, and FDG uptake was estimated with dynamic scanning. In a second group of five animals, PET scanning was performed 2 hr poststunning and repeated 24 hr later. RESULTS: In Group 1 animals, postischemic reductions were noted in both regional shortening and myocardial oxygen consumption. Myocardial blood flows at baseline were 0.72 +/- 0.05 ml/min/g in the LAD region and 0.83 +/- 0.07 ml/min/g in the non-LAD region; following reperfusion they were 0.70 +/- 0.07 ml/min/g and 0.89 +/- 0.08 ml/min/g, respectively. Within 2 hr of reperfusion, FDG retention was significantly lower in the LAD region compared with remote myocardium. As with Group 1, Group 2 also showed a reduction in FDG uptake in acutely reperfused myocardium relative to remote regions. Twenty-four hours later, FDG uptake within reperfused regions increased to 0.31 +/- 0.04 mumole/min/g and did not differ from remote myocardium. CONCLUSION: FDG uptake in acutely stunned swine myocardium is lower than remote regions at a time when regional myocardial blood flows are not dissimilar. This differs from 24 hr following reperfusion in which enhanced FDG uptake may be observed relative to perfusion. Therefore, the time course of metabolic changes following reperfusion needs to be considered in patients undergoing viability studies with PET.

Adenosine receptor blockade enhances myocardial stunning without a sustained effect on fluorine-18-FDG uptake postreperfusion.

UNLABELLED: The aim of this study was to determine whether adenosine receptor blockade before ischemia would enhance the degree of stunning and induce a sustained decrease in glucose uptake after reperfusion. METHODS: Stunning was induced in 14 anesthetized swine by partially occluding the left anterior descending artery (LAD) for 20 min (> 80% flow reduction). Seven animals were pretreated with the nonspecific adenosine receptor blocker 8-phenyltheophylline (8-PT; 5 mg/kg), which decreased reactive hyperemia by an average of 38%. Myocardial glucose uptake was assessed 1 hr following reperfusion with PET and the glucose analog 18F-fluorodeoxyglucose (FDG). RESULTS: Before ischemia, systolic shortening in the LAD region was 15% +/- 6% in the control group and 16% +/- 4% in the 8-PT group and in both groups was reduced to - 1% +/- 2% during ischemia. After reperfusion, systolic shortening was 7% +/- 3% in the control group and 2% +/- 3% in the 8-PT group (p < 0.05). Myocardial oxygen consumption before ischemia was 4.58 +/- 3.03 micromol/min/g in the control group and 4.44 +/- 1.83 micromol/min/g in the 8-PT group (ns) and neither were different after reperfusion. In the postischemic LAD region, myocardial glucose uptake was 0.18 +/- 0.15 micromol/min/g in the control group and was similar to that of the 8-PT group (0.17 +/- 0.08 micromol/min/g; ns). CONCLUSION: The nonspecific adenosine blocker 8-PT enhanced the degree of stunning when given before ischemia but did not induce a sustained effect on myocardial glucose uptake after reperfusion.

Evidence against a role for dopamine D1 receptors in the myocardium of the pig.

1. We investigated the presence of dopamine D1 receptors in the myocardium of anesthetized pigs using intravenous infusions of dopamine, alone and after alpha- and beta-adrenoceptor blockade and intracoronary infusions of the selective D1 receptor agonist, fenoldopam. 2. Intravenous infusion of dopamine (2.5, 5 and 10 micrograms kg-1 min-1 for 10 min, n = 6) caused dose-dependent changes in heart rate (from 94 +/- 6 to 132 +/- 10 beats min-1, P less than 0.05), the maximal rate of rise of left ventricular pressure (LVdP/dtmax; from 2280 +/- 170 to 4800 +/- 410 mmHgs-1, P less than 0.05), mean arterial blood pressure (from 87 +/- 5 to 62 +/- 3 mmHg) and systemic vascular resistance (from 40 +/- 4 to 28 +/- 2 mmHgl-1 min, P less than 0.05). The increases in heart rate and LVdP/dtmax were abolished when dopamine was infused after alpha- and beta-adrenoceptor blockade. The vasodilator response was, however, only minimally affected. 3. Intravenous infusions of dopamine decreased coronary vascular resistance from 0.90 +/- 0.06 to 0.53 +/- 0.07 mmHg ml-1 min 100 g (P less than 0.05). This action of dopamine was not observed when dopamine was infused after blockade of the alpha- and beta-adrenoceptors. 4. Pretreatment with alpha- and beta-adrenoceptor blockade had no effect or only slightly attenuated the dopamine-induced decrease in vascular resistance of the brain, kidneys, adrenals and small intestine. 5. In 7 animals, intracoronary doses of 0.04, 0.1, 0.2 and 0.4g kg1- min 1 of fenoldopam had no effect on coronary venous oxygen content, local myocardial oxygen consumption, coronary blood flow or coronary vascular resistance. However, systemic effects were observed at the highest two doses, as manifested by a drop in mean arterial blood pressure from 82 +/- 4 to 72 +/- 4mmHg (P < 0.05) due to peripheral vasodilatation (e.g. cerebral vascular bed). Heart rate, LVdP/dt,.,, regional myocardial segment length shortening and left ventricular end-diastolic pressure were not affected at these doses. In 2 animals the infusion rate was increased to 4jug kg1 min 1, but again there was no evidence for coronary vasodilatation. 6. We conclude that the intravenous infusion of dopamine after alpha- and beta-adrenoceptor blockade and the intracoronary infusion of fenoldopam provided no evidence for a major role of D1 receptors in the coronary circulation of pigs. The absence of any effect of the employed doses of fenoldopam on LVdP/dt.mx and on regional myocardial segment length shortening also indicates that fenoldopam does not exhibit any inotropic action in this species.

Myocarditis as a cause of primary right ventricular failure.

Patients with cardiomyopathy secondary to inflammatory myocarditis usually present with biventricular signs and symptoms. On occasion, the disease may progress focally, with left ventricular involvement predominating. This patient had elevated neck veins, edema, and a dilated right ventricle in the absence of left ventricular abnormalities. At autopsy, diffuse, transmural fibrosis of the right ventricle was found, consistent with end-stage myocarditis, with minimal disease of the left ventricle. This case emphasizes that the clinical manifestations of myocarditis can be limited to the right ventricle and should be considered in the differential diagnosis of right ventricular failure.

Cardiopulmonary support mitigates the effects of experimental myocardial ischemia.

The effectiveness of cardiopulmonary support (CPS) as a rescue method following failed angioplasty is unknown. The proximal left anterior descending (LAD) was occluded for 20 min in 21 dogs. Group 1 animals (n=15) were given CPS and group 2 animals (n=6) served as controls. During coronary occlusion, animals receiving CPS had increased mean arterial pressure (71+/- 12 vs 58+/-7 mm Hg), decreased left atrial pressure (3+/-3 vs 12+/-3 mm Hg), increased ischemic area blood flow (0.20+/-0.16 vs 0.02+/-0.04 mL/min/g) and myocardial oxygen consumption (0.014+/- 0.008 vs 0.003+/-0.006 mL O2/min/g), decreased remote area myocardial oxygen consumption (0.026+/-0.010 vs 0.091+/-0.047 mL O2/min/g), and an improved myocardial oxygen consumption index (0.60+/-0.33 vs 0.02+/-0.03) when compared with controls (p<0.05). During reperfusion (no CPS), group 1 animals had increased cardiac index (210+/-95 vs 117+/-46 mL/min/kg), renal blood flow (110+/-38% vs 53+/-45%), ischemic area blood flow (1.13+/-0.40 vs 0.58+/-0.27), and myocardial oxygen consumption (0.066+/-0.015 vs 0.032+/-0.018) when compared with controls (p<0.05). CPS improves oxidative metabolism in selective myocardial segments during coronary occlusion, promotes recovery of the postischemic myocardium, and results in improved peripheral circulation.

Granulomatous myocarditis. Diagnosis by endomyocardial biopsy and response to corticosteroids in two patients.

Granulomatous involvement of the myocardium is of uncertain etiology, rarely diagnosed premorbidly, and the response to therapy is unknown. We report two patients with granulomatous disease apparently isolated to the myocardium, one presenting with cardiac arrest secondary to ventricular tachycardia, one with heart block. In both cases, the clinical rhythm was substantiated by electrophysiologic studies and neither case had evidence of significant myocardial dysfunction. In both, treatment was instituted with orally administered prednisone. One patient died suddenly two months following onset of therapy. Limited autopsy demonstrated no evidence of granulomatous involvement of the myocardium. The other patient is alive without clinical arrhythmias on amiodarone therapy; however, inducible ventricular tachycardia persists. Repeat endomyocardial biopsy in this patient demonstrated no granulomatous disease. These cases are discussed and the literature reviewed.

The influence of perioperative myocardial infarction on long-term prognosis following elective vascular surgery.

STUDY OBJECTIVE: The present study was performed to determine the influence of a perioperative myocardial infarction on long-term mortality in patients who have undergone elective vascular surgery. STUDY DESIGN: This was a 4-year follow-up of patients who had undergone elective vascular procedures at a Veterans Affairs Medical Center. Between January 1989 and December 1990, 115 consecutive patients underwent surgery for either an expanding abdominal aortic aneurysm (AAA) (38%) or for pain in the lower extremities (62%). RESULTS: Vital status at 4 years postsurgery was determined for all patients. Thirty-day postoperative mortality was 3%, while estimates at 1, 2, 3, and 4 years were 19%, 26%, 35%, and 39%, respectively. Of the 45 patients who died within 4 years following surgery, the major causes of death were cardiac (40%), cancer (18%), cerebrovascular (13%), and peripheral vascular disease (11%). Univariate predictors of 1-year mortality on preoperative evaluation were an abnormal ECG, moderate or greater sized exercise thallium defect and left ventricular ejection fraction < or =40%, and a perioperative myocardial infarction. Univariate predictors of 4-year mortality were non-AAA surgery and diabetes mellitus. Perioperative myocardial infarction was a marginally significant independent predictor of 1-year mortality (p=0.06), while the need for non-AAA surgery was a strong independent predictor at 4 years. CONCLUSIONS: Cardiac mortality is the major cause of late death among patients undergoing elective vascular surgery. Although preoperative indicators of symptomatic coronary artery disease and nonfatal perioperative myocardial infarction identified those individuals at increased mortality in the first postoperative year, the extent of vascular disease at presentation may be a more important determinant of long-term survival. A randomized trial in such patients is needed to assess the best strategy for treating patients with coexistent coronary artery and vascular diseases.

Pseudoaneurysm formation with superior vena caval syndrome 7 years after aortic composite graft placement.

With the advent of the composite graft for combined aortic valve and ascending aortic root operations, post-operative bleeding complications have been reduced. Hemorrhage along the suture sites may occur as a late complication and rarely may originate from the coronary-aortic graft junction. We report a case of a massive pseudoaneurysm, seen as "superior vena caval syndrome," 7 years after operation.

Cardiovascular profile of the new dihydropyridine derivative S12968.

The cardiovascular profile of S12968 was evaluated in anaesthetized pigs, using cumulative 15-min i.v. infusions of 1.25, 2.5, 5, 10 and 20 micrograms.kg-1.min-1 (n = 7) or equal volumes of its solvent (n = 7). S12968 decreased mean arterial blood pressure from 94 +/- 4 to 66 +/- 3 mm Hg (P less than 0.05) and cardiac output from 2.7 +/- 0.2 to 2.2 +/- 0.2 l.min-1 (P less than 0.05), had no effect on heart rate and left ventricular end-diastolic pressure, but decreased maxLVdP/dt (maximal rate of rise in left ventricular pressure) by up to 35 +/- 3% (P less than 0.05). With doses higher than 10 micrograms.kg-1.min-1 transmural left ventricular blood flow increased by up to 49 +/- 22% (P less than 0.05), favouring the subepicardium over the subendocardium. Myocardial oxygen consumption decreased by 22 +/- 7 and 32 +/- 8% (P less than 0.05) during infusion of 10 and 20 micrograms.kg-1.min-1, respectively. Heart rate, left ventricular end-diastolic pressure and arterial blood pressure were not affected, but maxLVdP/dt (partially) and cardiac output returned to pre-drug values a during a 60-min post-infusion period. In conclusion, S12968 exhibited a negative inotropic effect at low doses. However, with higher doses and after discontinuation of the infusion, vasodilatation occurred, while the negative inotropy disappeared. It is possible that an active metabolite, acting preferentially on the vasculature, was responsible for the vasodilatation.

Prognostic value of dipyridamole sestamibi single-photon emission computed tomography and dipyridamole stress echocardiography for new cardiac events after an uncomplicated myocardial infarction.

A high-dose dipyridamole stress test (0.84 mg/kg in 6 minutes) with simultaneous sestamibi single-photon emission computed tomographic (SPECT) and echocardiographic imaging was performed in 89 patients before hospital discharge after an uncomplicated myocardial infarction. The aim of this study was to determine the prognostic value of these tests for new cardiac events and to compare the relative values of SPECT and echocardiography in a postinfarction dipyridamole stress test. Two years after infarction, nine patients (10%) had died, five patients (6%) had suffered a nonfatal reinfarction, and 14 patients (16%) had been readmitted to the hospital for a revascularization procedure. Cardiac death had occurred in 5 (10%) of 48 patients with a positive SPECT versus 4 (10%) of 41 with a negative SPECT (difference not significant) and in 6 (19%) of 31 with a positive echocardiogram versus 3 (5%) of 56 with a negative echocardiogram (p = 0.05). Cardiac death or reinfarction had occurred in 8 (17%) of 48 patients with a positive SPECT versus 6 (15%) of 41 with a negative SPECT (difference not significant) and in 6 (19%) of 31 with a positive echocardiogram versus 8 (14%) of 56 with a negative echocardiogram (difference not significant). Thus the predictive value of the dipyridamole stress test for new cardiac events after an uncomplicated myocardial infarction was limited, irrespective of the method used to detect ischemia. Reversible perfusion defects were identified more frequently than new wall motion abnormalities but did not predict late events. A positive dipyridamole echocardiogram was associated with a higher late mortality rate but did not predict other cardiac events.

Altered coronary flow reserve in the hypertrophied heart: implications for therapy.

Coronary flow reserve has been shown to be abnormally low in several models of left ventricular hypertrophy induced by long-standing pressure overload. Because the presence of hypertrophy is a risk factor for the development of subendocardial ischaemia and sudden death, efforts to restore alterations in flow reserve may prove beneficial. In the following review, we discuss potential mechanisms which might contribute to this abnormal vasodilator capacity in the hypertrophied heart, with particular emphasis on how chronic therapy may potentially reverse such abnormalities. In addition, we report how the acute administration of various classes of pharmacological agents can alter measurements of coronary flow reserve, as observed in our anaesthetised swine model. Such factors must be considered before interpreting any changes in coronary flow reserve in models of hypertrophy following chronic administration of drugs.