Left Ventricular Coronary Blood Flow Research Articles

Stimulation of soluble guanylate cyclase improves donor organ function in rat heart transplantation

Heart transplantation remains the definitive therapy of end-stage heart failure. Ischemia-reperfusion injury occurring during transplantation is a primary determinant of long-term outcome of heart transplantation and primary graft insufficiency. Modification of the nitric oxide/soluble guanylate cyclase/cyclic guanosine monophosphate signaling pathway appears to be one of the most promising among the pharmacological interventional options. We aimed at characterizing the cardio-protective effects of the soluble guanylate cyclase stimulator riociguat in a rat model of heterotopic heart transplantation. Donor Lewis rats were treated orally with either riociguat or placebo for two days (n = 9) in each transplanted group and (n = 7) in donor groups. Following explantation, hearts were heterotopically transplanted. After one hour reperfusion, left ventricular pressure-volume relations and coronary blood flow were recorded. Molecular biological measurements and histological examination were also completed. Left ventricular contractility (systolic pressure: 117 ± 13 vs. 48 ± 5 mmHg, p < 0.001; dP/dtmax: 2963 ± 221 vs. 1653 ± 159 mmHg/s, p < 0.001), active relaxation (dP/dtmin: −2014 ± 305 vs. −1063 ± 177 mmHg/s, p = 0.02; all at 120 µl of left ventricular volume), and alteration of coronary blood flow standardized to heart weight (2.55 ± 0.32 vs. 1.67 ± 0.22 ml/min/g, p = 0.03) were markedly increased following preconditioning with riociguat. Myocardial apoptosis markers were also significantly reduced in the riociguat pretreated group as well as the antioxidant markers were elevated. Pharmacological preconditioning with riociguat decreases ischemia-reperfusion injury and improves donor organ function in our animal model of heart transplantation. Therefore, riociguat might be a potential cardioprotective agent.

Changes in left ventricular function and coronary blood flow velocity during isocapnic hypoxia: A cardiac magnetic resonance imaging study

Changes in left ventricular function and coronary blood flow velocity during isocapnic hypoxia: A cardiac magnetic resonance imaging study

906 Aortic elastic properties and left ventricular diastolic dysfunction in patients with obstructive sleep apnea

Although the responsible mechanisms are not yet fully known, obstructive sleep apnea is associated with an increased risk for cardiovascular disease and events. The aorta is not only a conduit delivering blood to the tissues but is also an important modulator of the entire cardiovascular system, its elastic properties also affecting left ventricular function and coronary blood flow. The aim of this study was to determine left ventricular diastolic function and aortic elastic properties in patients with obstructive sleep apnea syndrome. Fourteen male patients with obstructive sleep apnea and 14 age- and body mass index-matched healthy male controls took part in the study as a control group. All subjects underwent echocardiographic examination; left ventricular cavity dimension, standard and tissue Doppler parameters, and aortic diameter (3 cm above aortic valve) at systole and diastole were measured. While the aortic stiffness index in patients with obstructive sleep apnea was significantly higher than that of the control group (4.5 ± 0.3 vs 2.1 ± 0.1, P = 0.001), the aortic distensibility index was found to be lower in this group compared with controls (2.4 ± 1.2 vs 3.9 ± 1.5 cm2 dynes−1 10−6, P = 0.009). Furthermore, peak velocity of myocardial systolic wave and peak velocities of myocardial diastolic waves in sleep apnea patients were lower than in controls. There was an association between aortic stiffness and the apnea hypopnea index (coefficient = 0.49, P = 0.002). We also found an inverse correlation between peak velocity of myocardial diastolic wave and aortic stiffness (coefficient = −0.43, P = 0.003), using multiple linear regression. Increased aortic stiffness that is associated with the severity of disease in patients with obstructive sleep apnea may lead to diastolic dysfunction of the left ventricle.

Coronary hemodynamic and ventricular responses to angiotensin type 1 receptor inhibition in SHR: interaction with angiotensin type 2 receptors.

This study was designed to determine the effects of angiotensin II type 1 (AT(1)) receptor inhibition on coronary hemodynamics and ventricular mass and hydroxyproline content and the additive effects of angiotensin II type 2 (AT(2)) receptor inhibition in spontaneously hypertensive rats (SHR). The selective AT(1) receptor antagonist candesartan (10 mg/kg per day) was administered alone or in combination with the AT(2) receptor antagonist PD 123319 (50 mg/kg per day) for 12 weeks. Control SHR received placebo for the same period. Left and right ventricular coronary blood flow, blood flow reserve, and minimal coronary vascular resistance were determined by using radiomicrospheres in male 35-week-old rats. Mean arterial pressure; total peripheral resistance; left and right ventricular, renal, and aortic weights; and hydroxyproline concentration were also determined. Candesartan reduced mean arterial pressure and left ventricular, renal, and aortic masses, as well as hydroxyproline concentration and minimal coronary vascular resistance of both ventricles. PD 123319 partially prevented the hypotensive effect of AT(1) receptor inhibition and reversed the effect on myocardial hydroxyproline concentration. These data suggest that AT(2) receptors contribute to the hypotensive and antifibrotic effects but not the coronary hemodynamic improvement or reduced left ventricular mass of AT(1) receptor inhibition in these adult SHR.

Angotensin II Type 2 Receptors Participate in Reducing Blood Pressure During Angiotensin II Type 1 Receptor Blockade But Do not Affect Cardiovascular Mass and Coronary Hemodynamics

P7 This study was designed to determine the role of AT 2 receptors in the beneficial cardiovascular effects of chronic AT 1 antagonism in spontaneously hypertensive rats (SHR). A selective AT 1 receptor antagonist, candesartan (10mg/kg/day) alone (CAND), or in combination with the selective AT 2 receptor antagonist PD 123319 (50g/kg/day) (CAND+PD) was given for 12 weeks to adult male SHR. Control SHR received placebo (PLACEBO) for the same period. Left ventricular coronary blood flow (CBF), flow reserve (CFR) and minimal coronary vascular resistance (MCVR) were measured using radiomicrospheres in 35-week old rats. Mean arterial pressure (MAP), peripheral resistance (TPR), left ventricular weight (LVI), and aortic weight (AWI)were also measured. The grater MAP in CAND+PD group compared with CAND suggests that AT 2 receptor stimulation was responsible, in part for the hypotensive effect of AT 1 receptor antagonism, although they did not contribute to improved coronary hemodynamics and reduced LV and aortic masses after selective AT 1 receptor inhibition.

Angotensin II Type 2 Receptors Participate in Reducing Blood Pressure During Angiotensin II Type 1 Receptor Blockade But Do not Affect Cardiovascular Mass and Coronary Hemodynamics

P7 This study was designed to determine the role of AT 2 receptors in the beneficial cardiovascular effects of chronic AT 1 antagonism in spontaneously hypertensive rats (SHR). A selective AT 1 receptor antagonist, candesartan (10mg/kg/day) alone (CAND), or in combination with the selective AT 2 receptor antagonist PD 123319 (50g/kg/day) (CAND+PD) was given for 12 weeks to adult male SHR. Control SHR received placebo (PLACEBO) for the same period. Left ventricular coronary blood flow (CBF), flow reserve (CFR) and minimal coronary vascular resistance (MCVR) were measured using radiomicrospheres in 35-week old rats. Mean arterial pressure (MAP), peripheral resistance (TPR), left ventricular weight (LVI), and aortic weight (AWI)were also measured. The grater MAP in CAND+PD group compared with CAND suggests that AT 2 receptor stimulation was responsible, in part for the hypotensive effect of AT 1 receptor antagonism, although they did not contribute to improved coronary hemodynamics and reduced LV and aortic masses after selective AT 1 receptor inhibition.

Effect of ligation of spleen vessels on left ventricular function and coronary blood flow in dogs injected with scorpion venom.

Scorpion sting may cause myocardial dysfunction in human victims, probably by increased O2 demand and decreased O2 supply. In dog, scorpion venom (SV) causes no myocardial dysfunction. Myocardium is probably protected by "autotransfusion" of blood from the spleen to the circulation, increasing coronary blood flow (CBF) and O2 delivery. We hypothesized that ligation of spleen vessels prior to injection of SV in dogs would prevent the autotransfusion of blood, thereby causing myocardial ischemia due to decreased CBF, simulating the hemodynamic pattern of human envenomation. We studied cardiac output (CO), CBF, left ventricular (LV) O2 delivery and contractility in 11 dogs injected with 0.07 mg/kg of SV (Leiurus quinquestriatus). Ligation of spleen vessels was performed on 6 of the 11 dogs prior to SV injection. 15 min after SV injection CO had increased by 186% in control dogs, while ligation of spleen vessels completely prevented CO elevation (p<0.001). In both groups, however, LV dp/dt increased by 400% and dp/dt/p by 170% (p<0.001). CBF increased by 350% and 550% in the spleen and control groups (p<0.001) respectively. This was associated with elevation of diastolic blood pressure and a decrease in coronary vascular resistance. LV O2 delivery increased (p<0.05) in both groups. At 60 minutes there was a decrease in CO, stroke work, and LV end systolic pressure in both groups, while LV contractility remained above baseline. Scorpion venom injection in dogs causes an initial increase in CO by auto-transfusion of blood from the spleen. Prevention of the autotransfusion does not preclude increases in CBF, O2 delivery and LV contractility.

Beneficial effects of the T- and L-type calcium channel antagonist, mibefradil, against exercise-induced myocardial stunning in dogs.

Abnormalities in calcium homeostasis such as calcium overload have been shown to participate in the pathogenesis of myocardial stunning. The goal of this study was to investigate the effects of mibefradil, a mixed T- and L-type calcium channels antagonist on exercise-induced ischemia (i.e., high-flow ischemia). Nine dogs were permanently instrumented to measure left ventricular wall thickening (Wth) and coronary blood flow (Doppler). Infusion of saline or mibefradil (30 and 40 microg/kg/min, i.v., for 20 min) was started 10 min before exercise (10 min, 14 km/h; slope, 13%) and stopped at its end. Circumflex coronary artery stenosis (pneumatic occluders) was set up 5 min before exercise to suppress exercise-induced increase in mean coronary blood flow without simultaneously affecting Wth at rest. Mibefradil (30 microg/kg/min) was also administered at the beginning of the recovery period in a subset of four dogs. During exercise with saline, Wth was dramatically reduced (-77 +/- 7%; p < 0.05) and recovered only after 24 h. Mibefradil at both doses significantly limited tachycardia during exercise (211 +/- 7 and 210 +/- 5 beats/min vs. 240 +/- 8 beats/min for mibefradil, 30 microg/kg/min, mibefradil, 40 microg/kg/min, and saline, respectively) but exerted no negative inotropic effects. Mibefradil at both doses significantly reduced the intensity of myocardial stunning and the time to recovery in Wth (3 h). Administration of mibefradil at the beginning of the recovery period did not protect against myocardial stunning. Administration of a mixed T- and L-type calcium channel antagonists before ischemia confers cardioprotection against exercise-induced myocardial stunning. This may potentially be related to the limitation of exercise-induced tachycardia and/or the prevention of calcium overload.

Right ventricular function in chronically anemic fetal lambs

OBJECTIVE: Our purpose was to determine whether the increase in extravascular fluid in chronic fetal anemia occurs either because of heart failure or despite successful cardiac adaptation. STUDY DESIGN: Right ventricular function curves were obtained in five ovine fetuses at the start, midpoint, and end of 5 to 8 days of anemia induced by isovolemic daily hemorrhage. Least-squares fit of the ascending and plateau lines of stroke volume versus right atrial pressure were used to establish breakpoints (intersection of the ascending and plateau lines), which were compared by analysis of variance for repeated measures. Myocardial blood flow was measured by microspheres. RESULTS: Carotid arterial oxygen content was reduced from 7.0 ± 0.3 to 2.1 ± 0.1 ml/dl and the hematocrit from 29% ± 1.8% to 13% ± 0.6%. Breakpoint analysis of function curves showed that although right atrial pressure remained unchanged (3.4 ± 0.7 and 3.6 ± 0.6 mm Hg) stroke volume increased from 1.03 ± 0.14 to 1.62 ± 0.25 ml/kg. Both right and left ventricular coronary blood flow were increased, 1351 ± 313 and 1166 ± 264 ml/min per 100 gm. Excess fluid was present in the abdomen and chest of most animals at autopsy. CONCLUSION: Tissue edema during severe anemia occurs despite normal right atrial pressure, increased stroke volume, and markedly increased coronary blood flow, markers of successful cardiac adaptation. (A M J O BSTET G YNECOL 1996;174:1289-94.)

Effects of inspiratory loading on left ventricular myocardial blood flow and metabolism

With airways obstruction, mean pleural pressure decreases. It has been postulated that associated increases in left ventricular afterload increase myocardial O2 demand (MvO2) and coronary blood flow (CBF). We tested this hypothesis in 12 anesthetized mixed-breed dogs. Through a median sternotomy, dogs were instrumented for the measurement of mean arterial pressure, cardiac output, and left anterior descending CBF. A catheter placed in the coronary sinus allowed sampling of left ventricular venous blood. MvO2 was calculated as CBF x (arteriovenous content difference), and coronary resistance was calculated as (mean arterial pressure)/CBF. After closure of the thoracotomy, animals were studied before and during inspiratory threshold loading (IL) of -20 to -25 cmH2O while breathing 100% O2 before and after bilateral cervical vagotomy. During IL, heart rate fell [approximately 20 beats/min (NS prevagotomy, P less than 0.05 postvagotomy)], arterial PCO2 increased [45 to 66 Torr prevagotomy, 45 to 50 Torr postvagotomy (P less than 0.01)], and arterial O2 content was unchanged. CBF increased with IL:41% prevagotomy (P less than 0.01), 18% postvagotomy (P less than 0.02). However, with IL, MvO2 did not increase significantly either pre- or postvagotomy. Coronary resistance decreased with IL [30% prevagotomy, 24% postvagotomy (P less than 0.01)]. In eight dogs, PCO2 was increased by increasing dead space while the animals were mechanically ventilated and paralyzed. Although there was little change in CBF, heart rate fell by an amount equal to that with IL. We conclude that 1) IL causes coronary vasodilation not related to changes in MvO2, PCO2, or vagal tone; 2) MvO2 does not increase with IL; and 3) decreased heart rate with IL is related to hypercapnia and/or acidosis.

Recovery of oxygen utilization efficiency after global myocardial ischemia

The time required for myocardial oxygen utilization to recover from 12 minutes of warm ischemia was studied in 15 sheep. Five control animals had 42 minutes of cardiopulmonary bypass at 37 °C with the heart beating and vented. In 10 experimental animals, the aorta was clamped for 12 minutes during bypass with the heart vented, and the animals were perfused 30 additional minutes after removal of the clamp. In both groups, measurements of left ventricular coronary arterial blood flow, oxygen consumption (LVO 2), peak systolic pressure, circumferential systolic stress integral (CSI), and pressure volume area (PVA) were made 30 minutes after and hourly for 5 more hours after cardiopulmonary bypass ended. Reversible ischemia significantly increases the relationship between LVO 2/PVA and LVO 2/ CSI 1 hour after the clamp is released, but the relationships return to prebypass values by 2 hours. Ischemia significantly decreases end-systolic elastance, which remains depressed thereafter. Cardiopulmonary bypass without myocardial ischemia significantly decreases total ventricular mechanical energy output and oxygen utilization efficiency of the working sheep heart but does not significantly alter end-systolic elastance or the LVO 2/ PVA and LVO 2/CSI relationships. Twelve minutes of warm ischemia impairs oxygen utilization efficiency in the reperfused sheep heart for more than 60 minutes but less than 120 minutes.

Alterations of coronary blood flow and reserve with aging in Fischer 344 rats.

To determine whether aging affects the coronary circulation, left and right ventricular coronary blood flow and vascular resistance at rest and after maximal vasodilation were measured by left atrial injection of radioactive microspheres in conscious, unrestrained male Fischer 344 rats at 4, 12, and 20 mo of age. As a function of age, maximal coronary blood flow per 100 g of tissue decreased by 43% in the left ventricle at both 12 and 20 mo, whereas a 44 and a 47% reduction was found in the right side of the heart at the same time intervals. Minimal coronary vascular resistance per 100 g of myocardium increased by 56 and 36% in the left ventricle and by 48 and 44% in the right at 12 and 20 mo, respectively. No change was found in total minimal coronary resistance for either ventricle despite an increase in myocardial mass. Maximal coronary blood flow per 100 g to the endocardium was depressed more than epicardial flow, leading to a 24% reduction in the endocardial-to-epicardial flow ratio at 20 mo. Coronary vascular reserve per 100 g, expressed as the increase in coronary blood flow during maximal coronary vasodilation, was greater in the right than in the left ventricle at all ages. It is concluded that the changes in coronary hemodynamics associated with maturation and aging are comparable with those seen in pressure overload hypertrophy with an increased vulnerability potential of the myocardium to ischemic episodes, particularly of the subendocardial region of the left ventricle.

Calcium reverses global and regional myocardial dysfunction caused by the combination of verapamil and halothane.

In order to evaluate the effects of the combination of halothane and verapamil on left ventricular function and coronary blood flow (CBF), six sheep were anaesthetized with halothane (1.2% inspired) and given increasing cumulative doses of intravenous verapamil. Regional myocardial function was assessed by sonomicrometry in the areas supplied by the left anterior descending coronary artery (LAD) and the left circumflex coronary artery (LC). Changes in global haemodynamics, atrioventricular conduction, LV relaxation and systolic shortening after 0.32 mg X kg-1 intravenous verapamil indicated impaired left ventricular function. Significant myocardial dysfunction (post-systolic shortening) occurred in the LAD territory, accompanied by a 64% decrease (42 +/- 6 to 15 +/- 3, P less than 0.01) in coronary perfusion pressure (CPP). Coronary blood flow in the LC segment decreased 83% (102 +/- 15 to 17 +/- 13, P less than 0.01) as coronary reserve was exhausted with the decrease in CPP. Calcium chloride reversed the impairment of global and regional myocardial function observed with verapamil, improved the impaired left ventricular relaxation, but did not significantly alter atrioventricular conduction. Thus the combination halothane-verapamil can cause significant left ventricular depression and myocardial dysfunction, possibly by inducing subendocardial ischaemia or by direct pharmacologic effect. Calcium chloride reverses this regional myocardial dysfunction as well as the deleterious global haemodynamic changes caused by halothane-verapamil; however, the changes in atrioventricular conduction are not corrected by calcium.

Effects of calcium entry blockade on left ventricular dynamics in exercising dogs.

To study the previously undefined effects of calcium entry blockade on left ventricular (LV) function and coronary blood flow during dynamic exercise we gave intravenous equihypotensive infusions of nifedipine (10 +/- 4 SE micrograms X kg-1 X min-1), diltiazem (60 +/- 8 micrograms X kg-1 X min-1), and verapamil (52 +/- 7 micrograms X kg-1 X min-1) before and after intravenous propranolol (2 mg/kg) to chronically instrumented dogs at rest and while running on a treadmill at 4 and 10 km/h. Prior to beta-blockade, each agent significantly and equivalently (P = NS among drugs) reduced mean arterial pressure during exercise (-13% nifedipine, -8% diltiazem, -15% verapamil at 4 km/h, each P less than or equal to 0.01 vs. exercise alone) but did not significantly alter LV end-diastolic dimension (EDD), heart rate, or cardiac output compared with exercise alone. Only verapamil blunted the positive inotropic response to exercise (LV dP/dtmax decreased 20% at 4 km/h, P less than 0.01 vs. exercise alone). Coronary blood flow was significantly and equivalently increased at rest and during submaximal exercise with each calcium blocker, but this effect was largely offset by propranolol. During exercise after beta-blockade each agent produced significant additional reductions in mean arterial pressure and dP/dtmax at peak exercise but did not alter LVEDD or heart rate compared with results obtained with propranolol alone. Combined beta-blockade and verapamil uniquely diminished myocardial contractility to a greater extent at peak exercise than at rest (dP/dtmax 1,260 +/- 410 peak exercise vs. 1,775 +/- 431 mmHg/s rest, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Ethanol impairs cardiocirculatory function in treated canine hemorrhagic shock.

This study examined the hypothesis that ethanol-induced alterations in cardiac function and regional blood flow impair recovery from shock after resuscitation. Blood ethanol levels 45 minutes after ethanol (3 gm/kg) was administered intrajejunally were 276 +/- 30 mg/100 ml (N = 14 dogs). Twelve dogs received saline solution and served as control animals. Elevated blood ethanol levels increased the rate of left ventricular pressure rise (+763 +/- 80 mm Hg X sec) and coronary blood flow (+0.77 +/- 0.18 ml X min X gm), decreased respiration, and caused a significant metabolic acidosis (arterial pH, 7.25 +/- 0.02; arterial lactate, 1.5 +/- 0.07 mmol/L). Two hours of hemorrhagic shock impaired cardiovascular function and regional blood flow to a similar extent in all dogs. Volume replacement (shed blood and lactated Ringer's solution, 50 ml/kg) transiently improved cardiac performance in the ethanol group. Two hours after volume replacement, a lower cardiac output, stroke volume, stroke work, myocardial oxygen efficiency, and persistent acidosis occurred in the intoxicated dogs (p less than 0.05) despite adequate coronary perfusion. Myocardial sensitivity to acidosis after shock may account for the reduced cardiac function in the ethanol group. However, it is possible that shock aggravated ethanol-induced pancreatic ischemia and contributed to impaired cardiocirculatory function in postinfusion shock.

Regional blood flow changes in response to near maximal exercise in ponies: A review

In recent years, increasing attention has been focused on the physiological responses of the horse to maximal exercise. Cardiovascular response in near maximally exercised galloping ponies (heart rate 225 +/- 7 beats/min; whole body oxygen consumption 122 +/- 12 ml/min/kg) comprised a marked increase in blood flow to the cerebellum, myocardium, diaphragm and the working muscles, while renal blood flow decreased precipitously. Cerebral and brainstem perfusion did not vary from resting values. Transmural homogeneity of myocardial blood flow persisted during near maximal exercise. It was reported that tachycardia of exercise contributed about one-third of the total increment in left ventricular coronary blood flow. Considerable unutilised coronary vasodilator capacity was also demonstrated in near maximally exercised ponies and it was suggested that maximally exercising ponies were not limited from further exertion because of the coronary circulation.

Effect of hypoxia on the normal and ischemic myocardium.

This study investigated the effect of hypoxia on global and regional myocardial function in the normal heart and in the heart with a critically constricted coronary artery. Eight dogs under halothane anesthesia were subjected to progressive degrees of hypoxia while global and segmental heart function as well as general hemodynamics were evaluated. In the control phase of the experiment, the coronary circulation was undisturbed. A decrease in the inspired oxygen fraction from 0.3 to 0.1 was associated with significant increases in the heart rate, cardiac output, left ventricular minute work and coronary blood flow, and significant decreases in systemic vascular resistance. regional myocardial function (measured by endocardial fiber shortening) did not change. In dogs with a critical constriction applied to the left anterior descending coronary artery (LAD), hypoxia significantly increased heart rate and decreased stroke volume. Indices of global myocardial function did not change, but regional function in the area supplied by constricted LAD was depressed during severe hypoxia. This study implies that measured indices of global heart function bear little relation to regional function when a compromised segment of the myocardium is subjected to hypoxia.

The relationship between the perfusion deficit, infarct size and time after experimental coronary artery occlusion.

It is well known that coronary occlusions of short duration do not produce infarcts in the dog heart, but permanent occlusions always do. The aim of this paper was to investigate with quantitative direct measurements the determinants of infarct size within these two extremes. We measured left ventricular MV2, coronary and collateral blood flow and infarct size after occlusion times varying between 45 minutes and 24 hours. MVO2 was kept low in one group by establishing low heart rates with a synthetic opiate. In another group, MV2 was kept elevated by giving synthetic catecholamines (dobutamine) that stimulated contractility and heart rate. Under the described experimental conditions LV-coronary blood flow reflected the true demand for blood and oxygen. The ratio of collateral blood flow over coronary blood flow (both measured with tracer microspheres) was therefore a good approximation of the supply-demand ratio (SD). Since collateral flow was inhomogeneously distributed across the left ventricular wall, the SD-ratio showed similar variations. As the collateral blood flow increased with elapsed time after coronary occlusion, the SD-ratio improved. Since high LV-O2-demand increased coronary flow but exerted practically no influence on collateral flow, this situation influenced the SD-ratio in a negative way. Decreased O2-demand had the opposite effect. The SD-ratio is thus a valid expression of the relative and absolute blood flow deficit as influenced by the local and general O2-demand. We found significant and characteristic correlations between the SD-ratio and infarct which was only influenced by time. A blood flow deficit of 90% (i.e., collateral flow = 10% of required flow) produced a 50%-infarct (relative to the risk-region) with a 45-min occlusion but a 90%-infarct with occlusion times of 3 hrs and longer. If the perfusion deficit is only 0.5 (collateral flow = 50% of required flow), no infarct is detectable at occlusion times shorter than 3 hrs. Small perfusion deficits of only 20% below required flow caused infarctions at 24 hrs and longer. In the group where the SD-ratio was closer to unity because of a low overall LV-O2-consumption (bradycardia), infarcts at t = 24 hrs were significantly smaller than in the group with a high LV-MVO2.

Static exercise in anesthetized dogs, a cause of reflex alpha-adrenergic coronary vasoconstriction.

The coronary blood flow and vascular resistance responses to static hindlimb exercise were studied in 11 anesthetized dogs after beta- and combined alpha- and beta-adrenergic blockade to determine if this stress causes coronary vasoconstriction. After beta-blockade static exercise increased the blood pressure and double product, but decreased the right and left ventricular (LV) coronary blood flow and increased the coronary vascular resistance. These vascular changes primarily occurred in the epicardial and mid-myocardial but not the endocardial layers of the LV. Following combined alpha- and beta-adrenergic blockade, the systemic hemodynamic and coronary flow and resistance changes were abolished. These data suggest that alpha-adrenergic mediated coronary vasoconstriction occurs during static hindlimb exercise in dogs.

Effects of intensive exercise training on myocardial performance and coronary blood flow.

Five instrumented and eight noninstrumented dogs were progressively trained for 12-18 wk on a motor-driven treadmill. Data were compared with 14 instrumented and 8 noninstrumented control dogs. Gastrocnemius malate dehydrogenase activity was significantly increased in the trained dogs (887 +/- 75 vs. 667 +/- 68 mumol . g-1 . min-1). The trained dogs also showed significant increases in maximum work capacity, cardiac output (7.1 +/- 0.5 vs. 9.1 +/- 0.7 1/min), stroke volume (25.9 +/- 2.0 vs. 32.0 +/- 2.0 ml/beat), and left ventricular (LV) positive dP/dtmax (9,242 +/- 405 vs. 11,125 +/- 550 Torr/s). Negative dP/dtmax was not significantly different. Peak LV systolic pressure increased with exercise, but there was no significant difference between the trained and control dogs. LV end-diastolic pressure did not change with exercise and was the same in both groups. Tension-time index was lower in the trained dogs at rest and submaximum exercise (9.7 km/h, 10%) but was not different at maximum exercise. Diastolic pressure-time index was significantly higher in the trained dogs at rest and during submaximum exercise but was not different at maximum exercise. LV coronary blood flow was significantly reduced at rest (84 +/- 4 vs. 67 +/- 6 mo . min-1 . 100 g-1) and during submaximum exercise (288 +/- 24 vs. 252 +/- 8 ml . min-1 . 100 g-1). During maximum exercise flow was not significantly different (401 +/- 22 vs. 432 +/- 11 ml . min-1 . 100 g-1) between the control and trained groups. The maximum potential for subendocardial flow was unchanged with training despite the development of mild hypertrophy.