ISCHEMIC impairment of left ventricular function plays a central role in the pathophysiology of ischemic heart disease (Page et al, 1971). Investigators have known for many years that loss of left ventricular contractile function occurs rapidly after coronary artery occlusion (Tennant and Wiggers, 1935). However, the quantitative interrelationships between regional left ventricular function and coronary flow are not well understood. The present study was performed to delineate the relationships between regional left ventricular ischemia, regional alterations in left ventricular function, and the corresponding extent of myocellular necrosis.Previous investigators have documented the temporal and geometric changes in regional myocardial blood flow (RMBF) after coronary artery occlusion

SUMMARY The effect of i.v. dobutamine on acute myocardial ischemic injury was assessed in 22 anesthetized dogs subjected to serial 10-minute occlusions of the left anterior descending coronary artery. The severity of ischemic injury was determined by mass spectrometric measurement of the increase in intramural carbon dioxide tension (zAPmco2) in the ischemic zone. In the nine protocol 1 dogs, dobutamine, 20 ,ug/kg/min, infused between the control and final occlusion, significantly increased both heart rate (HR) and left ventricular (LV) dP/dt; APmco2 was significantly higher during the dobutamine infusion than during control occlusion (76 ± 21 vs 56 + 13 mm Hg,p < 0.01). The nine protocol 2 dogs were atrially paced at a HR of 20-30 beats/min above baseline values during the control occlusion and received dobutamine (12.6 ± 7.8 ugg/kg/min) at doses necessary to attain an equal HR (mean 149-154 beats/min) during the last occlusion.Although LV dP/dt was higher after dobutamine, APmco2 was similar during the two occlusions. Protocol 3 dogs (n = 4) received lower doses of dobutamine (5.6 ± 3.2 Ag/kg/min) to produce an increase in LV dP/dt, but not in HR compared with baseline values; APmco2 was similar during control and dobutamine occlusions. There were no major changes in arterial or left atrial pressures. Rate-pressure product, an indirect measurement of myocardial oxygen consumption, was increased only by the higher doses of dobutamine in protocol 1.Thus, inotropic stimulation with dobutamine during coronary occlusion does not cause important augmentation of acute myocardial ischemic injury in the nonfailing heart unless HR is increased simultaneously.THE SEVERITY of evolving acute myocardial ischemic injury can be influenced by interventions performed before or shortly after experimental coronary artery occlusion.' Pharmacologic agents and hemodynamic alterations can affect ischemic injury. Although most reports deal with interventions that lessen myocardial ischemic injury, certain interventions can intensify ischemia or increase infarct size.2 B Even though the role of specific therapy to protect ischemic myocardium in the patient with evolving acute myocardial infarction is not clear, it is widely held that interventions that augment ischemic injury in experimental animals should be avoided in patients with myocardial ischemic syndromes.0" 11 Most deleterious influences on evolving ischemic damage are thought to be mediated by further alterations in the relationship between myocardial oxygen supply and demand in ischemic tissue. An creasing heart rate, contractile state, or left ventricular (LV) wall tension.'1 Because many studies that showed augmentation of ischemic injury used interventions that simultaneously alter several determinants of myocardial oxygen demand or supply or both, we investigated whether deleterious effects on ischemic damage also result from more selective alterations in these hemodynamic variables.Methods Twenty-two mongrel dogs that weighed 17-44 kg were anesthetized with i.v. pen...

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SUMMARY Hypertension and atherosclerotic coronary arterial obstruction frequently coexist in patients. However, the effect of increased aortic pressure on ischemic segmental dysfunction is not well understood. We studied the effects of aortic pressure increases on segmental left ventricular function during myocardial ischemia. Eighty-two dogs instrumented with three to six pairs of pulse-transit piezoelectric crystals were studied in an awake, unsedated state to measure segmental wall thickness. A pneumatic balloon occluder was positioned around the proximal left anterior descending artery (LAD). Thirty-three dogs underwent LAD occlusion and served as normotensive controls (group A). Group B dogs (n = 23) received a 6-hour infusion of phenylephrine (PE) beginning 5 minutes after LAD occlusion to increase aortic diastolic arterial pressure to 120-130 mm Hg; aortic pressure was then allowed to return to normal for the subsequent 18 hours. The eight dogs in group C received a 6-hour infusion of PE, but no coronary arterial occlusion was produced. In group D (n = 12), distal constriction of the thoracic aorta was maintained for 24 hours after LAD occlusion. Regional myocardial blood flow (RMBF) was measured with radioactive microspheres in six conscious dogs and both RMBF and intramyocardial Pco2 were measured in seven open-chest dogs to assess alterations in regional myocardial oxygen supply and demand. Segments of myocardium were arbitrarily grouped according to the amount of net systolic thickening (NET) present 5 minutes after LAD occlusion and before increasing aortic pressure: group 1 retained 67-100+% of control NET, group 2 047%, and group 3 less than 0% (paradoxic motion). In dogs receiving PE plus LAD occlusion and in dogs with aortic constriction and LAD occlusion, NET was transiently depressed in groups 1 and 2 compared with the normotensive cohort; 24 hours after occlusion, NET in groups 1, 2 and 3 did not differ significantly from that in the normotensive dogs. Systemic hypertension resulted in a significant increase in endocardial and midwall RMBF and, in seven open-chest dogs, decreased the intramyocardial accumulation of carbon dioxide after LAD occlusion. Increased aortic pressure in dogs without coronary occlusion produced reversible decreases in end-diastolic wall thickness, NET and LV dP/dt. Thus, the production of systemic hypertension with diastolic pressures of 110-120 mm Hg acutely or for 6 hours during evolving canine myocardial infarction does not appear to exert an important deleterious effect on myocardial oxygen supply and demand. However, 24 hours of mildly increased aortic pressure accentuates end-diastolic wall thinning in segments with paradoxic systolic motion and results in a failure of their return to control values at this period.PHYSICIANS frequently encounter patients with ischemic heart disease in whom the myocardial oxygen supply/demand ratio is altered by systemic arterial hypertension. For example, uncontrolled hypertension may provoke episodes of angina in patients with c...