Myocardial Demand Research Articles

Effects of dobutamine on left ventricular performance and myocardial metabolic demands in patients with ischemic heart disease.

Sixteen patients with coronary artery disease undergoing cardiac catheterization were studied. Eleven had previous infarcts and the patients were divided into two groups: In group I were 7 patients with no left ventricular dysfunction, no increase in ventricular size, or symptoms of congestive failure; group II included 9 patients with ventricular dysfunction, increased ventricular size, and 7 of the 9 had congestive failure. Each patient underwent a continuous infusion of dobutamine from 2.5 to 10 micrograms/kg min-1 with dosage increments of 2.5 micrograms/kg at 15-minute intervals. Systemic and coronary hemodynamic measurements were obtained at the end of the 5 and 10 micrograms/kg min-1 infusion doses. Left ventricular performance improved (higher cardiac index, left ventricular stroke work index and mean systolic ejection rate, and lower left ventricular end-diastolic pressure), while heart rate, mean arterial pressure, and coronary sinus blood flow increased after dobutamine in the 16 patients. While patients in both groups had a rise in cardiac index, a reduction in left ventricular end-diastolic pressure, an unchanged mean arterial pressure and a rise in coronary blood flow, only patients in group I had a significant increase in heart rate, and only patients in group II had significant increases in left ventricular stroke work index and mean systolic ejection rate, and a significant reduction in systemic vascular resistance. Left ventricular oxygen consumption did not increase significantly in either group. However, 5 patients showed a decreased myocardial lactate extraction after 10 micrograms/kg min-1 of intravenous dobutamine, 3 from group I and 2 from group II.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of the pericardium in the regulation of myocardial blood flow and its distribution in the normal and acutely failing left ventricle of the dog.

The effects of the pericardium on the amount and distribution of left ventricular myocardial blood flow were studied. In 10 normal dogs, transfusion of blood from a donor dog resulted in modest increases in coronary flow and ventricular diameter that were greater with an open than a closed pericardium. The ratio of subendocardial to subepicardial flow remained normal with or without the pericardium, at low and high diastolic ventricular pressure, and before and after pharmacological vasodilation with chromonar. In 18 dogs, cardiac failure was induced by constant infusion of the metabolic inhibitor, phenformin. Modest ventricular dilatation occurred if the pericardium was open. A progressive rise in myocardial blood flow developed in those with the pericardium open (1.06 rising to 3.02 ml . g-1 . min-1). A lesser increase (0.62 to 1.75 ml . g-1 . min-1) was seen in dogs with the pericardium closed; they selectively increased subendocardial flow, producing an average subendocardial to subepicardial flow ratio of 2.25. Pharmacological vasodilatation then resulted in uniform transmural flow. The pericardium can influence myocardial flow indirectly by influencing myocardial metabolic demand, when the heart is stressed. It may have a beneficial role in preventing the increased oxygen and coronary flow requirements produced by ventricular dilatation.

Consistent parallel relationships among myocardial oxygen consumption, coronary blood flow, and pericardial infusate adenosine concentration with various interventions and beta-blockade in the dog.

Coronary blood flow responds uniquely to changes in myocardial demand, regardless of the stimulus. If adenosine mediates this response, interstitial fluid adenosine concentration should also change in parallel with myocardial oxygen consumption and coronary blood flow during alterations of cardiac work. We tested this hypothesis by measuring coronary blood flow, myocardial oxygen consumption, and the concentration of adenosine in pericardial infusates, an index of interstitial fluid adenosine concentration, during six experimental conditions and control states in anesthetized, open-chest dogs. Significant alterations of myocardial oxygen consumption and coronary blood flow during aortic constriction, vagal stimulation, atrial pacing, or intravenous infusion of calcium chloride, norepinephrine, or isoproterenol were accompanied by significant alterations in pericardial infusate adenosine concentration. Significant linear relationships were determined among myocardial oxygen consumption, coronary blood flow, and pericardial infusate adenosine concentration for each of the experimental stimuli and their paired control values. There were no significant differences among the six different conditions for any of these relationships. In addition, these relationships were not altered by beta-blockade in five dogs subjected to aortic constriction and calcium infusion. Although beta-blockade may alter the effects of a stimulus, myocardial oxygen consumption, coronary blood flow, and adenosine all are affected proportionately. The results suggest that adenosine production responds to alterations of myocardial oxygen consumption independently of the stimulus which produces the change in oxygen demand, and the resultant change in interstitial fluid adenosine concentration may initiate the change in coronary blood flow to maintain the balance between oxygen supply and demand.

Alpha-adrenergic regulation of the coronary circulation in the conscious dog

To examine the role of neural and humoral factors in the control of coronary vasoactivity in conscious animals in which the complicating effects of general anesthesia and recent surgery were absent, dogs were instrumented with miniature pressure gauges in the aorta and left ventricle to measure aortic and left ventricular pressures and with flow probes in the left circumflex coronary artery to measure coronary blood flow. Several weeks after recovery from operation, experiments were conducted in the conscious dogs. Stimulation of the carotid chemoreceptor reflex elicted a biphasic response; initially striking reflex coronary vasodilation was observed: Coronary blood flow tripled even after changes in metabolic factors were minimized by pretreatment with propranolol. The chemoreceptor reflex coronary vasodilation was mediated both by cholinergic activation and withdrawal of alpha-adrenergic tone. The second phase of the response involved an increase in coronary vascular resistance, associated with elevated arterial pressure and an absolute reduction in coronary blood flow and coronary sinus oxygen content. The later period of coronary vasoconstriction was abolished by alpha-adrenergic blockade. Intravenous infusion of the alpha-adrenergic agonist methoxamine increased mean arterial pressure by 65 ± 5% and total coronary vascular resistance by 92 ± 14%. To determine whether the large coronary arteries were also under autonomic control, the dogs were instrumented with a pair of ultrasonic crystals on opposing surfaces of the left circumflex coronary artery to measure its diameter directly and continuously. Methoxamine reduced coronary cross-sectional area substantially, thereby constricting large coronary arteries and resistance coronary vessels. Thus, while the coronary arteries are regulated by changes in myocardial metabolic demands, they are also responsive to changes in neural stimuli. The most striking changes were observed with augmentation and withdrawal of alpha-adrenergic constrictor tone, which appear to be important in the control of large as well as small coronary vessels.

Effects of verapamil on coronary hemodynamic function and vasomobility relative to its mechanism of antianginal action

The effect of intravenous verapamil on systemic and coronary hemodynamic function was studied at cardiac catheterization in 12 patients with coronary artery disease. Verapamil was administered as a 2-minute bolus (0.145 mg/kg) followed by an infusion (0.005 mg/kg/min). Cardiac output and coronary sinus blood flow were measured by thermodilution techniques. Caliber of the large coronary arteries and of diseased segments was determined from the coronary angiogram using a computer-assisted method. Verapamil reduced mean arterial pressure 14% (p less than 0.001), systemic vascular resistance 21% (p less than 0.01), and stroke work index 16% (p less than 0.001). Coronary vascular resistance decreased 24% (p less than 0.01) with a small increase in coronary sinus blood flow (+13%, difference not significant [NS]). Myocardial oxygen consumption determined in 5 patients showed no significant change with verapamil. Luminal area in 39 coronary lesions was measured in the "normal" portion of the diseased segment and at its maximal constriction, and an estimate of flow resistance in the stenosis was computed. Overall, 50% of "normal" and of diseased coronary segments dilated significantly with verapamil. Stenosis dilation resulted in an average 14% reduction (p less than 0.01) in estimated flow resistance. In 8 patients, the luminal changes (n = 27) induced by sublingual nitroglycerin were compared with those induced by verapamil. Nitroglycerin induced a significantly greater increase in coronary caliber in both normal and diseased segments; estimated stenosis flow resistance decreased 28% with nitroglycerin compared with 14% with verapamil (p less than 0.01). Thus, verapamil moderately dilates the systemic and coronary small vessel resistance bed without apparently increasing myocardial metabolic demand. Furthermore, verapamil mildly dilates large coronary conductance vessels in both "normal" and diseased segments, although significantly less than does nitroglycerin.

The Role of Clonidine In Hypertensive Heart Disease: Influence on Myocardial Contractility and Left Ventricular Afterload

The hemodynamic and contractile effects of clonidine were studied in hypertrophied hearts of spontaneously hypertensive rats (Okamoto-Aoki strain, SHR). The hemodynamic pattern was characterized by dose-dependent decreases in systolic blood pressure and systolic wall stress, ie, the afterload imposed upon the left ventricle, whereas left ventricular ejection fraction and stroke volume were unchanged. Even at extremely high doses (10(-5)M/L) there was found no depression of isometric tension development and maximum isotonic shortening velocity of the isolated LV papillary muscle. It is concluded that clonidine may be beneficial in hypertensive heart disease, if ventricular unloading associated with a reduction in myocardial energy demand is desired.

Effect of brief periods of paced ventricular tachycardia on coronary blood flow in dogs before and after graded coronary stenosis.

The effect of short bouts (1 min) of electrically induced ventricular tachycardias (VT) of increasing rates (160-240/min) was studied in 8 anesthetized dogs before and after graded constrictions of the left anterior descending (LAD) and the circumflex (CCA) coronary arteries. In the absence of coronary stenosis, paroxysmal VT caused a significant decrease in tension-time index (TTI), coronary blood flow (CBF) and coronary vascular resistance (CVR). Single and combined coronary stenosis caused relatively small alterations of the VT-induced depression of the systemic hemodynamics but reversed the effect of paroxysmal VT on the CVR. In the presence of single 90% LAD stenosis, VT resulted in an increase in CVR-LAD and a decrease in F-LAD associated with a fall in CVR-CCA and a rise in F-CCA. Combination of 90% LAD plus 70% CCA stenosis abolished the compensatory fall of CVR-CCA resulting in a pronounced reduction of F-CCA during VT. The results support the concept that in the presence of severe coronary stenosis brief paroxysmal ventricular tachycardias do increase myocardial nutritional demand but rather decrease nutritional supply.

Effects of acute vagally-mediated bradycardia on systemic hemodynamics and coronary blood flow before and after coronary stenosis.

The effects of short episodes (1 min) of vagally-mediated bradycardia were studied in 9 anesthetized dogs utilizing vagal stimulation and slow atrial pacing (120 and 80 beats/min) before and after graded coronary constriction of the left anterior descending (LAD) and the left circumflex (CCA). In the presence of 90% LAD stenosis, bradycardia tended to restore both the elevated total LAD coronary vascular resistance (CVR-LAD) and the reduced, total CVR-CCA towards control levels obtained at corresponding slow rates in the absence of coronary stenosis; as a result, LAD coronary flow (F-LAD) was relatively less reduced and the accessory rise of F-CCA disappeared. In the presence of combination of 90% LAD plus 70% CCA stenosis, the effects of bradycardia on total CVR-LAD and F-LAD were similar to those obtained with single 90% LAD stenosis, but the accessory flow through the CCA was abolished resulting in no significant difference of the rate-dependent alterations of total CVR-CCA and F-CCA as compared with those observed in the absence of coronary stenosis. In the presence of single or combined coronary stenosis, bradycardia restored the depressed aortic pressure and cardiac output towards control values obtained at comparable slow rates before coronary stenosis. The results support the concept that in the presence of 90% LAD stenosis vagally-mediated bradycardia 1) decreases the tension-time index (myocardial nutritional demand) shifting cardiac performance to less expensive "flow work" and 2) facilitates antegrade flow through the highly stenotic LAD thereby inhibiting accessory flow through the nonstenotic CCA.

The early pathophysiologic understanding of angina pectoris

Caleb Hillier Parry of Bath and Allan Burns of Glasgow formulated explanations of angina pectoris that stand as brilliant early examples of pathophysiologic reasoning. These astute observers proposed the concept that symptomatic ischemic heart disease results from a dynamic imbalance of myocardial energy supply and demand. Their work forms the basis of our traditional understanding of effort-related chest pain in obstructive coronary artery disease.

Regional myocardial blood flow and oxygen delivery in fetal, newborn, and adult sheep.

We measured and calculated their product, regional myocardial oxygen delivery, in unanesthetized, previously instrumented fetal, newborn, and adult sheep. In the fetus, blood flow and oxygen delivery were greater to the right ventricular free wall than to the left ventricular free wall. In the left ventricular free wall oxygen delivery increased significantly after birth and later decreased to a level in the adult that was similar to that of the fetus. There was a progressive decrease in oxygen delivery to the right ventricular free wall during the developmental period that we studied. Although the inner-to-outer blood flow ratio was significantly lower for the left and right ventricular free walls of the fetuses as compared with the newborns and adults, the ratio was greater than one in all three groups for both of the ventricular free walls. These data demonstrate that the changes that occur in the circulation after birth are associated with significant alterations in right and left ventricular myocardial blood flow and oxygen delivery, which most likely reflect changes in regional myocardial metabolic demands. In addition, there are further significant changes in regional myocardial blood flow during the transition from the newborn to adult hemodynamics.

Postoperative monitoring of myocardial oxygen tension: experience in 51 coronary artery bypass patients.

Following a preliminary feasibility report, polarographic monitoring of myocardial tissue O2 tension (Pmo2) in 51 coronary bypass patients has been accomplished. In this context, the influence of rapid atrial pacing (RAP), O2 inhalation, and intra-aortic balloon assistance (IAB) was statistically analyzed using Wilcoxon sign-rank and Student's t-tests. Electrodes were implanted in revascularized and nonrevascularized areas for comparison (24.0 +/- 1.1; and 26.3 +/- 1.8 mmHg Pmo2, p, not significant). Increasing myocardial O2 demand with RAP caused a 6% PmO2 drop (p less than 0.01). A 70% O2 inhalation increased Pmo2 by 30% (p less than 0.01). In 5 cases the benefit of IAB was confirmed by a 41% increase in Pmo2 (p = 0.02). These data support the clinical usefulness of polarographic Pmo2 as a measure of regional myocardial oxygenation. In addition to early recognition of intraoperative or postoperative graft failure previously reported, the efficacy of various therapeutic interventions can be more precisely determined.

Insulin infusion in conscious dogs. Effects on systemic and coronary hemodynamics, regional blood flows, and plasma catecholamines.

Cardiovascular actions of insulin were studied by intravenous infusions of insulin (4 and 8 mU/kg per min) in normal conscious dogs. This resulted in increases in cardiac output, heart rate, and left ventricular derivative of pressure with respect to time (dP/dt) and dP/dt/P, as blood glucose was reduced. The inotropic and chronotropic effects of insulin were not related to hypoglycemia, as they persisted even when blood glucose was restored to control values or when it was prevented from falling by a simultaneous infusion of glucose. These cardiac effects were accompanied by increases in plasma catecholamines, and were abolished by propranolol pretreatment. Both plasma epinephrine and norepinephrine increased during insulin hypoglycemia, but only norepinephrine increased during insulin infusion when euglycemia was maintained. Mean arterial blood pressure did not change significantly during insulin hypoglycemia, but rose if euglycemia was maintained, probably due to the selective increase in norepinephrine in the latter condition. A pressor response also occurred in propranolol-pretreated dogs during insulin hypoglycemia, but was abolished when the animals also had been pretreated with phentolamine, indicating that the vasoconstrictor action of insulin was mediated via alpha adrenergic receptors. Insulin infusion increased left ventricular work and myocardial blood flow in dogs with and without hypoglycemia. Myocardial blood flow, however, did not change significantly during insulin infusion in dogs pretreated with propranolol. As propranolol also diminished the inotropic response, it appears that the increase in myocardial blood flow caused by insulin in the normal dog is causally related to the increased myocardial metabolic demand. Insulin also produced vasomotor effects on other vascular beds. In skeletal muscle, blood flow was increased under all study conditions, except during insulin hypoglycemia after propranolol-pretreatment when unopposed alpha-mediated vasoconstriction was present. The persistent increase in flow during both alpha and beta adrenergic blockade suggests that insulin has a direct dilator effect on skeletal muscle vasculature. In the adrenal gland, flow was increased except during euglycemia, when no rise in plasma epinephrine was observed, suggesting coupling between adrenal flow and catecholamine release. In the splanchnic bed, flow was decreased during euglycemia, when plasma norepinephrine rose, and during beta adrenergic blockade with propranolol, when unopposed alpha-mediated vasoconstriction also predominated. A similar pattern was found in the kidney, except that renal blood flow also fell after combined alpha and beta adrenergic blockade. The results show that the vasomotor effects on regional flows are mediated both via adrenergic mechanisms, and in the case of skeletal muscle and kidney, via mechanisms unrelated to sympathetic stimulation.

Fetal myocardial oxygen and carbohydrate consumption during acutely induced hypoxemia.

Two days after catheter placement we measured the heart rate, arterial blood pressure, myocardial blood flow, and the myocardial consumption of oxygen, glucose, lactate, and pyruvate in 11 fetal sheep in utero. We then administered 8-10% oxygen to the ewe, producing a 50% decrease in oxygen content in the fetal ascending aortic blood. After 15 min of hypoxemia we repeated the measurements. Oxygen content in the fetal coronary sinus blood decreased significantly, but the arteriovenous difference of oxygen across the left ventricle also decreased during hypoxemia. Fetal myocardial blood flow increased 160% above the control level, and the myocardial oxygen consumption did not change. The systolic arterial blood pressure increased and the heart rate decreased, but cardiac work, as estimated by the rate-pressure product, was unchanged. As both fetal myocardial oxygen consumption and cardiac work did not change, myocardial oxygenation, the relationship between oxygen consumption and cardiac work, appears to be unchanged during this degree of hypoxemia. Although arterial blood glucose, lactate, and pyruvate concentrations increased significantly during hypoxemia, only the myocardial consumption of pyruvate increased; the arteriovenous difference of glucose and lactate decreased in proportion to the increase in myocardial blood flow. During hypoxemia, glucose consumption did not change, and lactate continued to be consumed rather than produced; thus it is apparent that fetal myocardial metabolism continued to be aerobic during this degree of hypoxemia. Complete oxidative combustion of the quantities of carbohydrates that were consumed would supply all of the substrate necessary to meet fetal myocardial energy demands both at rest and during hypoxemia.

Isoproterenol-induced myocardial dysfunction in dogs with coronary stenosis.

Stress-induced regional myocardial ischemia in the presence of mild coronary stenosis was studied in five dogs 2-4 wk after implantation of pairs of ultrasonic crystals to measure left ventricular wall thickening (% delta WT) and subendocardial segmental shortening (% delta L). Isoproterenol (0.2 micrograms.kg-1.min-1) was infused before and after production of coronary stenosis, which produced no resting dysfunction. During isoproterenol infusion with coronary stenosis % delta WT and subendocardial % delta L were significantly decreased although blood flow was comparable to conditions at rest, indicating that the demand for blood flow exceeded supply. Linear regression analysis of mean transmural blood flow versus % delta WT during isoproterenol demonstrated that wall thickening was significantly related to changes in mean blood flow: y (percentage wall thickening) = 27.5 X (transmural blood flow) -8.2 (r = 0.83); likewise % delta L was significantly related to subendocardial blood flow during isoproterenol infusion: y (percentage shortening) = 17.1 X (subendocardial blood flow) -0.4 (r = 0.85). These results indicate that both regional % delta WT and % delta L sensitively reflect the adequacy of myocardial perfusion even during stress-induced changes in myocardial O2 demands and blood flow.

The effects of cibenzoline, an imidazoline derivative with antiarrhythmic properties, on systemic hemodynamics and regional myocardial performance

AbstractThe effects of increasing doses of cibenzoline (‐2(2,2‐diphenylcyclopropyl)‐2‐imidazoline, Cipralan), a new compound with antiarrhythmic properties, on systemic hemodynamics and regional myocardial performance were studied in anesthetized pigs. Doses of 0.5–2.0 mg kg−1 i.v. produced a 10–15% prolongation of the PP' interval, and a dose‐dependent increase (up to 60%) in QRS width, with only minor changes in PQ and ST length. Stroke volume decreased dose dependently (20–35%) immediately after drug administration, due to a decrease in myocardial contractility and an increase in systemic vascular resistance. Renal blood flow was unchanged, despite the decrease in cardiac output. Coronary blood flow decreased, while myocardial O2 extraction was unchanged. Hence myocardial O2 consumption decreased parallel to the decrease in flow, a consequence of the lowered myocardial O2 demand. Studies with radioactively labeled microspheres revealed that the decrease in myocardial blood flow was equally distributed over the transmural layers.

Adaptive changes of pyruvate oxidation in perfused heart during adrenergic stimulation.

Pyruvate oxidation was studied in isolated guinea pig hearts perfused under various conditions of work and stimulated by norepinephrine. Hearts metabolized pyruvate alone or in combination with 3-hydroxybutyrate or acetate as substrate. [1-14C]-pyruvate-dependent 14CO2 release into the venous effluent (MVpyr) was, like myocardial oxygen consumption (MVO2), directly related to aortic pressure or filling pressure. At high aortic pressures, ventricular pressure development and not work performance was the major determinant of MVO2 and thus MVpyr. With 1 mM pyruvate as sole substrate, 0.08 microM norepinephrine produced parallel changes in hemodynamic performance, MVO2. MVpyr, and pyruvate dehydrogenase complex (PDC) activity (active form). Similar and dose-dependent effects of norepinephrine were observed during infusion of 5 mM DL-3-hydroxybutyrate as cosubstrate. When 1 mM acetate was applied, MVpyr was also dependent on work performance and norepinephrine stimulation. However, in perfusions with 25 mM potassium chloride, norepinephrine did not enhance hemodynamic function or MVO2 and hence PDC activity and MVpyr. Thus regulation of the PDC in catecholamine-stimulated heart appears to be linked predominantly to myocardial energy demand even when alternative energy-providing substrates are utilized.

Effects of nifedipine on myocardial energy balance in experimental coronary vasoconstriction and occlusion.

The effect of nifedipine on the myocardial energy demand--supply imbalance caused by vasopressin-induced vasoconstriction, coronary occlusion, and their combined action was studied in isolated perfused rabbit hearts using the method of NADH fluorometry. Nifedipine (0.015 microgram/ml) completely prevented the development of NAD/NADH imbalance caused by coronary vasospasm. The role of vasoconstriction as an addition to coronary occlusion was very small in the development of regional energy imbalance and the vasopressin-induced detrimental effect was prevented by nifedipine. Energy imbalance caused by the occlusion alone was only partially improved by the drug. There was a delay in the development of energy imbalance and reduction in the final degree of NADH fluorescence response to the occlusion (97 +/- 8% vs. 66 +/- 9%, p less than 0.05).

Exercise-induced Myocardial Oxygen Supply-demand Imbalance in Asymptomatic or Mildly Symptomatic Aortic Regurgitation

Left ventricular (LV) performance may remain normal in patients with LV volume overload from aortic regurgitation, but this entity results in progressive LV dysfunction. Impairment of myocardial reserve may remain undetected by current methods of assessing ventricular performance at rest, but the stress of exercise may demonstrate a reduction of myocardial reserve. To analyze the relationship between the myocardial supply and demand for oxygen in patients with aortic regurgitation, the ratio of the diastolic pressure-time index (DPTI) over the systolic pressure-time index (SPTI) was derived from recordings of pressure tracings during cardiac catheterizations in 14 patients with aortic regurgitation, and this ratio was compared with that of 24 normal subjects. The patients with aortic regurgitation had a DPTI/SPTI that fell with exercise (0.91 +/- 0.2 to 0.55 +/- 0.2) to lower values than did the ratio in the normal subjects (1.3 +/- 0.2 to 0.8 +/- 0.1) with stress. Among the patients with aortic regurgitation, a DPTI/SPTI ratio less than 0.50 with exercise identified two groups of patients that were not well separated by more common indices of severity of aortic regurgitation. The only other parameter that separated these two groups was the end-systolic volume, which is an index that reflects myocardial contractile function independent of preload. The DPTI/SPTI ratio that falls to abnormal levels with exercise may accurately reflect a failure of myocardial reserve in aortic regurgitation.

Regulation of large coronary arteries by increases in myocardial metabolic demands in conscious dogs.

In order to assess the effects of increasing myocardial metabolic demand on the large epicardial coronary arteries, we measured left circumflex coronary artery diameter (ultrasonic transit time technique) and blood flow in conscious dogs with chronically implanted transducers. Myocardial oxygen consumption was increased by pacing-induced tachycardia and aortic constriction, and monitored by multiplying left circumflex coronary arterial blood flow by coronary arterio-venous oxygen content difference. Increase of heart rate by 90 beats/min caused myocardial oxygen consumption to increase by 34 +/- 4.3% (1 SEM); coronary blood flow at constant arterial pressure to increase by 32 +/- 6.8%; and coronary diameter to increase by 0.07 +/- 0.01 mm, P less than 0.01. Aortic constriction, producing a 53 +/- 5.1% increase of left ventricular systolic pressure, caused myocardial oxygen consumption to increase by 49 +/- 7.2%, coronary blood flow to increase by 50 +/- 6.0%, and coronary diameter to increase 0.03 mm, P less than 0.01. The increases in coronary artery diameter were gradual, not immediate, in onset and not altered by beta-adrenergic blockade. Thus, increased myocardial metabolic demand dilates large epicardial coronary arteries, but with a slower response time than the rapid dilation of the smaller resistance vessels.

Isometric Exercise and the Cardiovascular System.

In brief: There is little evidence that isometric exercise benefits the cardiovascular system, and many physicians believe that it imposes undue demands on the myocardium, so they prohibit such exercises for middle-aged or coronary disease patients. This review article examines the validity of this conclusion by summarizing the effects of isometric exercise on heart rate, blood pressure, myocardial demand, cardiac output, peripheral blood flow, and left ventricular function. Dr. Fardy concludes that isometric exercise is less hazardous than has been presumed and says guidelines should be established according to each patient's history.