Blood Flow Debt Repayment Research Articles

Reduced vasodilator response of the right coronary artery to myocardial ischemia in the hypertrophied right ventricle.

The reduced reactive hyperemic response of the right coronary artery (RCA) to brief coronary occlusion was assessed in dogs with pressure-induced right ventricular hypertrophy (RVH). Right coronary reactive hyperemia was observed in normal dogs and in dogs with pressure-induced RVH. RVH was induced by chronic pulmonary artery banding in eight 3- to 6-month-old dogs, and reactive hyperemia responses to coronary occlusion lasting for 5, 10, 15, 20, 30, 45, and 60 sec were compared to those in normal dogs. In dogs with RVH, the peak reactive flow rate and excess blood flow debt repayment after the release of 5- to 60 sec RCA occlusion were markedly attenuated. The calculated minimum coronary resistance was higher in RVH dogs than in normal dogs (p < 0.02). The occlusion time that produced one-half of the maximum %PRHc, T1/2, was significantly (p < 0.01) shorter in RVH dogs than in normal dogs, where %PRHc = (peak reactive flow rate baseline flow rate)/(baseline flow rate). T1/2 in RVH dogs varied inversely with right ventricular systolic pressure. Therefore, blood flow in the RCA in RVH is characterized by an attenuated flow response to acute myocardial ischemia, suggesting inadequate development of the coronary vasculature supplying the hypertrophied ventricle.

Effects of coronary occlusion duration on reactive hyperemia in conscious dogs and ponies

Coronary reactive hyperemia duration (RHD) and coronary blood flow debt repayment (BFDR) were compared in conscious dogs and ponies instrumented with coronary artery Doppler flow probes and pneumatic occluders. Additional ponies were instrumented with pacing electrodes. With the use of a Latin square design, eight animals of each species were subjected to a randomized series of nine coronary occlusions ranging from 5 s to 2 min in duration. In both species, postocclusion blood flow velocity rose rapidly and plateaued at similar peak levels relative to control, but in ponies this plateau lasted significantly longer. The interspecies difference in plateau duration increased as a function of coronary occlusion duration (COD). RHD ranged from 19.5 +/- 5.9 to 139.7 +/- 5.9 s in dogs and from 26.6 +/- 9.0 to 395.0 +/- 9.0 s in ponies. The slope of the RHD vs. COD curve was steeper in ponies. BFDR was similar in dogs and ponies at the shortest COD (418.1 +/- 26 vs. 451.4 +/- 58%) but declined in dogs as a function of COD to 232.3 +/- 26%. In ponies, BFDR increased as a function of COD to a maximum of 945.4 +/- 58% with a 60-s occlusion and then declined to 614.3 +/- 58%. RHD was not significantly altered in ponies when heart rate was changed to match that in dogs. Although the underlying basis for these interspecies differences in RHD and BFDR was not determined, the differences were considered to be too large to be explained by animal model differences in coronary conductance, collateral blood flow, or myocardial oxygen consumption.(ABSTRACT TRUNCATED AT 250 WORDS)

Opening of coronary collaterals by repeated brief coronary occlusions in conscious dogs.

The collateral blood flow and regional myocardial function during a one-minute coronary occlusion were compared before and after multiple one-minute coronary occlusions. After repeated coronary occlusions, the collateral blood flow velocity increased significantly from 0.7 +/- 0.1 (SE) to 2.0 +/- 0.2 cm/sec (p less than 0.05), and the blood flow debt repayment decreased from 326 +/- 26% to 189 +/- 12% (p less than 0.05). The systolic segment shortening in the collateral dependent zone improved slightly. Thus, the native coronary collateral vessels open in response to a repeated ischemic stimulus.

Effects of glyceryl trinitrate on functionally regressed newly developed collateral vessels in conscious dogs.

The effects of glyceryl trinitrate on collateral blood flow and regional myocardial function during a 2 min coronary occlusion were evaluated in 10 conscious dogs with well developed collateral vessels. Collateral growth was promoted by brief, repeated, reversible coronary occlusions. After partial regression in collateral function a small dose of glyceryl trinitrate (5 micrograms.kg-1) was injected intravenously 1 min before coronary occlusion. After pretreatment with glyceryl trinitrate the collateral blood flow velocity (mean[SD]) increased from 3.0(0.9) to 4.4(1.4) cm.s-1 (p less than 0.05). After 2 min of occlusion the percentage systolic subendocardial segment shortening in the collateral dependent zone increased from 7.8(6.1) to 12.6(6.7)% (p less than 0.05). The blood flow debt repayment after release of the occlusion decreased from 122(41) to 68(34%) (p less than 0.05). Thus in conscious dogs with regressed newly developed collaterals a major component of the beneficial effects of glyceryl trinitrate on collateral circulation is dilatation of collateral vessels, as evidenced by a pronounced increase in collateral blood flow and myocardial function during a transient period of coronary occlusion.

Electrocardiographic evaluation of collateral development in conscious dogs

In seven conscious dogs, endocardial ST-segment changes within the central ischemic area at 2 min after coronary occlusion were compared with the amount of reactive hyperemia and collateral blood flow. With the use of ultrasonic dimension gauges implanted in the subendocardium perfused by the left anterior descending coronary artery (LAD) and left circumflex coronary artery (LCCA), endocardial electrocardiograms and regional myocardial dimensions were simultaneously measured. Collateral vessels were developed by repeated 2 min LCCA occlusions during three weeks. Blood flow debt repayment following the release of LCCA occlusion was measured using a Doppler flowmeter. The collateral blood flow from LCCA to the area supplied by the occluded LAD was measured as a stepwise reduction in LCCA flow upon the release of LAD occlusion. With the attenuation of myocardial ischemia due to the collateral development, endocardial ST-segment shift revealed earlier restoration compared with subendocardial function. In the presence of mild ischemia, the ST-segment was still elevated. Thus, endocardial ST-segment changes serve as an indirect functional index of collateral development as well as regional myocardial function and blood flow debt repayment.

Effects of nifedipine on coronary reactive and exercise induced hyperaemia.

The effects of nifedipine on coronary vasodilation were studied during reactive hyperaemia after a transient coronary occlusion and during active hyperaemia associated with graded treadmill exercise. Studies were performed in 10 chronically instrumented dogs in which left circumflex coronary artery flow was measured with an electromagnetic flowmeter and myocardial oxygen extraction was determined from indwelling aortic and coronary sinus catheters. Thirty minutes after administration of nifedipine (10 micrograms.kg-1 iv), when coronary blood flow, arterial pressure, and heart rate had returned to control values, the vasodilatation following a 10 s coronary occlusion was significantly blunted, so that reactive hyperaemia blood flow debt repayment (mean(SEM)) was reduced from 387(39)% during control conditions to 270(33)% after nifedipine (p less than 0.05). In contrast, nifedipine did not alter the coronary vasodilatation that occurred in response to graded treadmill exercise so that the increase in coronary blood flow during exercise was not different from the control response. Thus, although nifedipine blunted ischaemic coronary vasodilatation during reactive hyperaemia, it did not alter coronary vasodilatation during active hyperaemia resulting from physiological increases of myocardial oxygen consumption.

Reactive hyperemia following one-beat coronary occlusions in the awake dog.

This study was performed to examine the effect of alterations of cardiac activity during brief coronary artery occlusions on the subsequent reactive hyperemic response. Reactive hyperemia following coronary occlusions equal in duration to one cardiac cycle were examined in 12 chronically instrumented awake dogs while heart rate was maintained constant by cardiac pacing. During continuous pacing, one-beat coronary occlusions resulted in reactive hyperemia with excess flow equal to 220 +/- 23% blood flow debt repayment. When coronary occlusions of identical duration were performed while a single cycle of pacing was omitted during the interval of occlusion, the subsequent reactive hyperemia was decreased. Conversely, when coronary occlusion was produced during the first potentiated beat following a single cycle of paired ventricular stimulation, the reactive hyperemia was increased. Since, in the absence of coronary occlusion, omitting a single paced beat caused a transient decrease in coronary flow, while a single cycle of paired ventricular stimulation caused a brief increase in coronary flow, the reactive hyperemic responses were corrected for these perturbations in flow. Despite these corrections, the influence of alterations of myocardial activity during the interval of occlusion persisted, with the decreased reactive hyperemia when occlusion occurred during an omitted beat and increased hyperemia when occlusion was performed during a potentiated beat. These data indicate substantial coupling between myocardial activity during coronary occlusions as brief as one cardiac cycle in duration and the subsequent reactive hyperemic response.

Effect of aminophylline on coronary reactive and functional hyperaemic response in conscious dogs.

This study was undertaken to determine whether adenosine release from myocardial cells plays a role in coronary reactive and functional vasomotion. Reactive hyperaemic blood flow responses to 10 s complete occlusions and 400 ms diastolic occlusions of the left circumflex coronary artery and to the vasomotor responses to the increased cardiac demand following ventricular extra-activation were examined in a chronic, heart-blocked dog preparation during a control period and following intravenous bolus administration of aminophylline (5 mg X kg-1). Aminophylline administration resulted in a 19% decrease in the blood flow debt repayment ratio of 10 s reactive hyperaemic responses compared with the control period. However, administration of aminophylline had no effect on the coronary vascular response to 400 ms diastolic occlusions or to ventricular extra-activations. These observations indicate that adenosine may play a role in the coronary vascular response to prolonged interventions but that other factors, as yet unidentified, may be implicated in the beat-to-beat regulation of coronary vascular resistance.

Effect of nitroglycerin and nifedipine on subendocardial perfusion in the presence of a flow-limiting coronary stenosis in the awake dog.

SUMMARY. This study examined the effects of nitroglycerin and nifedipine on the transmural distribution of myocardial blood flow when ischemia-induced vasodilation of the distal coronary vasculature caused a proximal coronary stenosis to become flow-limiting. Studies were performed in chronically instrumented awake dogs with electromagnetic flowmeter probes and hydraulic occluders on the left circumflex coronary artery. Myocardial blood flow was estimated with 15|i radioactive microspheres. During control conditions, subendocardial (endo) flow significantly exceeded subepicardial (epi) flow (endo:epi = 1.33 ± 0.12). Following a 10-second coronary occlusion, reactive hyperemia occurred with excess arterial inflow resulting in 330 ± 37% blood flow debt repayment. This response was not altered by nitroglycerin (0.015 mg/kg, iv), but was decreased by nifedipine (0.01 mg/kg, iv) to 175 ± 38%, indicating depression of the coronary vasodilator response to a brief ischemic stimulus. When, following a 10-second occlusion, arterial inflow was limited to the preocclusion rate by a proximal stenosis, subepicardial flow increased at the expense of hypoperfusion of the subendocardium (endo/epi decreased to 0.50 ± 0.04; P < 0.01), and the continuing subendocardial ischemia resulted in augmentation of the subsequent reactive hyperemia (debt repayment = 556 ± 5%; P < 0.01). Both nitroglycerin and nifedipine abolished the augmentation of the reactive hyperemic response which occurred when a total occlusion was followed by an interval of coronary stenosis. This effect was associated with enhanced subendocardial blood flow during the interval of restricted inflow, suggesting that both of these agents alleviate the subendocardial hypoperfusion and ischemia which occur in the presence of a proximal flow-limiting coronary stenosis. (Ore Res 50: 678-687, 1982)

Reduction of maximal coronary vasodilator capacity in conscious dogs with severe right ventricular hypertrophy.

Right coronary reactive hyperemia and the maximal coronary vasodilator response to adenosine were examined in conscious, normal dogs and dogs with right ventricular (RV) hypertrophy. RV hypertrophy was induced by chronic (5-7 months) pulmonary artery stenosis. With RV hypertrophy, RV weight to body weight ratio rose by 70% (P < 0.001), right coronary artery blood flow (Doppler ultrasonic technique) rose from 17 +/- 1 to 51 +/- 5 ml/min, and RV transmural blood flow (radioactive microsphere technique) increased from 0.78 +/- 0.06 to 1.62 +/- 0.10 ml/min per g, while the RV endocardial:epicardial perfusion ratio decreased from 1.36 +/- 0.04 to 1.0 +/- 0.02. Excess blood flow debt repayment following release of a 15-second right main coronary artery occlusion was attenuated markedly (P < 0.001) to 107 +/- 22% from the normal value of 325 +/- 41%. Maximal coronary vasodilator capacity (to iv adenosine) was reduced in the hypertrophied right ventricle, as reflected by a lower (P < 0.05) level of maximal transmural blood flow and a higher (P < 0.02) level of minimum coronary vascular resistance per gram of hypertrophied right ventricle compared to normal. During maximal coronary vasodilation, the endocardial:epicardial perfusion ratio decreased (P < 0.001) below unity in the hypertrophied right ventricle to a level (0.83 +/- 0.06) significantly lower (P < 0.001) than normal (1.16 +/- 0.03). Thus, the development of severe RV hypertrophy is characterized by an attenuated coronary response to acute ischemia and by a reduction in maximal coronary vasodilator capacity. We conclude that the increase in cardiac mass which results from chronic pulmonary artery stenosis is not accompanied by a proportionate increase in cross-sectional area of coronary vessels supplying the hypertrophied ventricle.

High energy phosphate stores and lactate levels in different layers of the canine left ventricle during reactive hyperemia.

To study postischemic recovery of myocardial energy metabolism in relation to the reactive hyperemic response, the tissue levels of creatine phosphate (CP), adenosine triphosphate (ATP), and lactate were estimated in the outer, middle, and inner layers of the left ventricle before, during, and at several times after a 20-second bilateral coronary arterial occlusion in the open-chest dog. The reactive hyperemic response was characterized by monitoring blood flow in the cannulated coronary sinus in a separate group of dogs. Substantial changes in myocardial CP and lactate, but not ATP, were produced by the occlusion and reciprocal transmural gradients in CP and lactate occurred such that CP was lowest and lactate was highest in the inner layer. Recovery of high energy phosphate stores (CP + ATP) occurred long before blood flow returned to the preocclusion level, this being achieved in two of the three layers after completion of only 29% of the reactive hyperemic response when the blood flow debt repayment was 151%. Lactate returned to control levels during the response, but recovery times in the different layers were delayed compared to those for the high energy phosphate stores. A transmural lactate gradient was maintained as the regional levels declined, and recovery times were different for each of the three layers, being longest in the inner layer. The results suggest that during the reactive hyperemic response (1) kinetically different processes are involved in the repletion of energy stores and the removal of anaerobically produced metabolites, and (2) metabolic vasodilation of coronary vessels probably is more pronounced and sustained longer in the inner than in the outer ventricular layer.

Myocardial reactive hyperemia caused by initial myocardial anoxia during aortic valve replacement

Reactive hyperemic response of individual coronary arteries and of the whole heart to anoxia during coronary cannulation was investigated in 10 patients undergoing aortic valve replacement. Reactive hyperemic response in man is identical to that reported in experimental investigations. The duration of hyperemic response was dependent on the length of the preceding period of anoxia; the longer the period of anoxia, the more prolonged was the hyperemic response. No significant collateral circulation between the coronary arteries could be demonstrated during prolonged anoxia of an individual coronary artery. Blood flow debt was almost always overpaid, but the repayment percentage decreased with the lengthening of the anoxic period, being 460 percent after a short period of anoxia (less than or equal to 2 minutes), 230 percent after an anoxic period of moderate length (3 to 5 minutes), and only 160 percent after a long period of anoxia (greater than or equal to 7 minutes). The total mean repayment of blood flow debt of the whole heart was 195 percent.

Effects of nitroglycerin on transmural myocardial blood flow in the unanesthetized dog.

This study was designed to determin the effect of nitroglycerin upon transmural distribution of myocardial blood flow in the awake dog during normal conditions and in the presence of ischemia-induced coronary vasodilation. Studies were performed in chronically prepared dogs with electromagnetic flowmeters and hydraulic occluders on the left circumflex coronary artery. Regional myocardial blood flow was estimated by using radionuclide-labeled microspheres, 7-10 mum in diameter, injected into the left atrium. During control conditions endocardial flow (0.86 plus or minus SEM 0.05 ml/min per g) slightly exceeded epicardial flow (0.72 plus or minus 0.03 ml/min per g, P smaller than 0.05), and this distribution of flow was not significantly altered by nitroglycerin. After a 5-s coronary artery occlusion, reactive hyperemia occurred with excess inflow of arterial blood effecting 360 plus or minus 15% repayment of the blood flow debt incurred during occlusion. When arterial inflow was limited to the preocclusion rate during coronary vasodilation after a 5-s total coronary artery occlusion, flow to the subepicardial myocardium was increased at the expense of underperfusion of the subendocardial myocardium, and the delayed reactive hyperemia was markedly augmented (mean blood flow debt repayment =775plus or minus 105%, P smaller than 0.01). Tese data suggested that subendocardial underperfusion during the interval of coronary vasodilation in the presence of a flow-limiting proximal coronary artery stenosis caused continuing subendocardial ischemia which resulted in augmentation of the reactive hyperemic response. In this experimental model both the redistribution of myocardial blood flow which occurred during an interval of restricted arterial inflow after a 5-s coronary artery occlusion and augmentation of the subsequent reactive hyperemic response were returned toward normal by nitroglycerin. This effect of nitroglycerin may have resulted, at least in part, from its ability to vasodilate the penetrating arteries which deliver blood from the epicardial surface to the subendocardium.

Blood flow from and oxygen uptake by muscle, during and after partial venous occlusion.

In dog gastrocnemius-plantaris muscle in situ, effects of partial venous occlusion and its release were compared to effects of arterial occlusion and release. During partial venous occlusion, blood flow decreases, arteriovenous oxygen difference is constant, and oxygen consumption is, therefore, reduced proportionately to blood flow. On release of partial venous occlusion, unlike release of arterial occlusion in which both blood flow debt and oxygen debt are repaid, there is little or no repayment of blood flow debt, arteriovenous oxygen difference remains constant, and there is, therefore, little or no repayment of oxygen debt. These effects of partial venous occlusion are reminiscent of those reported to occur during and after release of passive stretch of circulated muscle, and it is proposed that the stretch effect is secondary to venular occlusion. The observations are consistent with the hypothesis that, within limits, muscle oxygen consumption is dependent on or limited by blood flow.