Effects of KB-944, a novel calcium antagonist, in several models of canine myocardial ischemia

The actions of KB-944 ([4-(2-benzothiazolyl)-phenylmethyl]phosphonic acid diethylester) on hemodynamics and regional myocardial blood flow during partial or total coronary artery occlusion were studied in anesthetized dogs. In one series of experiments a severe stenosis, that reduced distal diastolic coronary perfusion pressure to 40 mm Hg, was applied to the left anterior descending coronary artery whereas in another series of experiments the left anterior descending was ligated to produce a total occlusion. Intravenous infusion of KB-944 (100 and 200 micrograms/kg/min) decreased heart rate and left ventricular systolic and aortic blood pressure. Total coronary artery blood flow and regional perfusion of normal myocardium were increased by KB-944 in both models. KB-944 increased regional segment function in normal and ischemic regions and maintained distal coronary artery perfusion pressure, coronary flow and transmural regional myocardial blood flow during partial coronary artery occlusion despite a reduction in aortic pressure. In a model of total coronary artery occlusion, KB-944 had no effect on the indirect indices of collateral function, retrograde flow and retrograde pressure. However, when diastolic aortic pressure was maintained, KB-944 produced transmural increases in myocardial blood flow to normal and collateral dependent zones. Thus, KB-944 maintains ischemic zone blood flow despite decreases in coronary perfusion pressure and increases in tissue flow in the collateral dependent region when aortic pressure is prevented from decreasing.     

Cardiac conditioning ameliorates cardiac dysfunction associated with renal hypertension in rats

To explore the effect of physiologic hypertrophy superimposed on pathologic hypertrophy, hearts from female control rats (C), renal hypertensive rats (H), rats conditioned with a 10-12 wk swimming program (Sw), and hypertensive rats trained by the swimming program (H-Sw) were perfused in an isolated working rat-heart apparatus. Systolic blood pressure was approximately 100 mmHg in C and Sw and was 160 mmHg in H and H-Sw. The swimming program had no effect on blood pressure. Compared with C, heart weight was increased by 30% in Sw, 47% in H, and 77% in H-Sw. At high preload and afterload, cardiac output (milliliters per gram dry LV weight) was decreased in H, increased in Sw, and partially restored towards normal in H-Sw. Ejection fraction, percent fractional shortening, and mean velocity of circumferential fiber shortening were enhanced in Sw, depressed in H, and normalized in H-Sw when compared with C. Coronary flow and myocardial oxygen consumption in this series of hearts were depressed in H, with no restoration in H-Sw, but coronary effluent lactate/pyruvate ratios were only elevated in the hearts of H-Sw. Coronary vascular responses were examined in a second series of experiments which used microspheres. In this series, the depressed coronary flow observed in H was partially restored towards normal in H-Sw and the inner/outer myocardial flow ratio was normal when hearts were perfused at 140 cm aortic pressure but was somewhat depressed in both H and H-Sw when the hearts were perfused at 80 cm aortic pressure. These studies demonstrate that hypertrophic hearts from renal hypertensive rats have diminished coronary flow and depressed cardiac function when they are studied in the isolated working heart apparatus, yet there is no evidence of myocardial ischemia. Superimposition of a chronic swimming program results in increased hypertrophy but restoration of cardiac function partially or completely to normal. Thus, pathologic and physiologic hypertrophy are biologically distinct entities. Physiologic hypertrophy may partially ameliorate the defects associated with pathologic hypertrophy.     

Effect of practolol on blood flow distribution in the myocardium during acute regional ischaemia in cats

The β-adrenergic blocking agent practolol was given to 11 cats with acute coronary artery ligation, and regional myocardial tissue blood flow was measured by the distribution of 15 μm labelled microspheres. Practolol reduced heart rate and cardiac contractility, but left ventricular end-diastolic pressure rose in eight animals. In three animals, however, the haemodynamics were essentially unchanged and these are referred to as non-responders. No changes in regional myocardial blood flow were observed after practolol administration, either in ischaemic, border or normal areas of the left ventricle. This indicates less serious imbalance between oxygen demand and delivery in ischaemic tissue. There was no endocardial/epicardial redistribution of tissue flow. Practolol did not appear to improve coronary perfusion, and beneficial clinical effects of practolol are therefore probably related to reduction of myocardial oxygen demands.     

Balance and imbalance of regional myocardial contractile function and blood flow

Summary During normoperfusion, both contractile function and myocardial blood flow are heterogeneously distributed throughout the left ventricle. Midwall segment shortening is greater at the apex than at the base of the left ventricle, and it is greater in the anterior than in the posterior wall. Also, transmural heterogeneity of myocardial deformation exists, with greater segment shortening and wall thickening in inner than in outer myocardial layers. Myocardial blood flow is greater in inner than in outer myocardial layers. Apart from transmural heterogeneities, there are adjacent regions with largely different resting flow in the same heart. While an increase in myocardial contractile function will lead to a metabolically mediated increase in myocardial blood flow, an increase in regional coronary perfusion within or above the autoregulatory range does not, in turn, increase regional myocardial contractile function. During hypoperfusion induced by a proximal coronary stenosis, the reduction in subendocardial blood flow is more pronounced than that in subepicardial blood flow, and contractile function in the inner myocardial layers ceases more rapidly than that in outer myocardial layers. The reduced regional myocardial contractile function is closely matched to the reduced regional myocardial blood flow; however, such coupling between reduced flow and function is lost when ischemia is prolonged for several hours, i.e., function for a given flow is further reduced. Acute embolization of the coronary microcirculation induces a progressive loss of regional myocardial function at unchanged regional myocardial blood flow, i.e., perfusion-contraction mismatch. During reperfusion, regional myocardial contractile function remains depressed for a prolonged period of time, depending on the severity, duration and location of the preceding ischemic epsiode, while regional myocardial blood flow is restored. Eingegangen: 24. Oktober 2000 /Akzeptiert: 22. M?rz 2001     

Effect of hyperglycaemia-induced hyperosmolality on heart function in the dog

Abstract. Changes in myocardial water content, left ventricular diastolic stiffness, cardiac performance, coronary blood flow, myocardial contractile force, rate of change of myocardial force, and peak acceleration of the aortic volume flow were examined in twenty-five dogs during glucose-induced hyperosmolality before and after pancreatectomy, the latter with and without insulin treatment. Glucose-induced hyperosmolality accounted for myocardial dehydration, increased diastolic stiffness and consequent decrease of left ventricular performance only in the absence of insulin, while coronary blood flow, myocardial contractile force, rate of change of myocardial force and peak acceleration of the aortic volume flow increased independently from the presence or absence of insulin during the glucose-induced hyperosmolality. These findings suggest that the frequent development of heart failure in hyperosmolar diabetic coma could partly be explained by myocardial dehydration and by the consequent decrease in left ventricular compliance and performance.     

冠心病左室结构与功能相关关系的临床分析

目的　探讨冠心病不同阶段的检查结果与心脏结构、功能关系。方法　通过对 2 2 6例患者临床资料的分析 ,对比心绞痛和心肌梗死对左室结构和功能的影响。结果　主动脉内径、左房内径、左室舒张期内径、舒张末期容积、收缩末期容积、每搏输出量、心输出量、平均室壁厚度和左室心肌质量等参数冠心病各组较正常组有增加的趋势而射血分数、左室短轴缩短率降低 ,收缩功能参数与心室结构变化有关 ;舒张早期血流的峰值流速随心肌损害加重而减低 ,舒张功能参数与冠状动脉严重程度密切相关。冠心病冠状动脉造影阴性损害也同样大。结论　冠心病人出现心室重构 ,收缩、舒张功能逐渐恶化。因此 ,控制心室重构意义重大。     

Myocardial Blood Flow Distribution in Concentric Left Ventricular Hypertrophy

Regional myocardial blood flow during both control conditions and ischemia-induced vasodilatation was studied in eight chronically instrumented awake dogs. Seven of these animals had coarctation-banding of the ascending aorta performed at 6 wk of age, and the other dog had congenital subvalvular aortic stenosis. The mean left ventricular weight for the group was 157+/-7.6 g, and the left ventricular body weight ratio was 8.76+/-0.47 g/kg. None of the animals exhibited signs of congestive heart failure.During the control state, the mean left ventricular systolic pressure was 249+/-12 mm Hg and the left ventricular end-diastolic pressure was 11.5+/-0.5 mm Hg. The aortic diastolic pressure was 74+/-6 mm Hg. Mean left circumflex coronary artery blood flow was 71+/-6 cm(3)/min. In the animals with coarctation-banding, 52+/-6% of the flow occurred during systole. In the dog with congenital subvalvular aortic stenosis, 5% of the coronary flow was systolic. Mean transmural blood flow during resting conditions was 0.97+/-0.08 cm(3)/min per g, and the ratio of endocardial to epicardial flow (endo/epi) was 0.88+/-0.07. During reactive hyperemia, the mean transmural blood flow increased to 3.5+/-0.30 cm(3)/min per g; however, the endo/epi decreased to 0.52+/-0.06.THESE STUDIES DOCUMENT A DIFFERENCE IN TRANSMURAL BLOOD FLOW DISTRIBUTION BETWEEN THE NORMAL AND THE HYPERTROPHIED LEFT VENTRICLE: during resting conditions, in the normal ventricle, the highest flow occurs in the endocardial layer, whereas in the hypertrophied ventricle, the highest flow is in the middle layers with the endocardial flow less than the epicardial flow. During ischemia-induced vasodilatation, the abnormal endo/epi becomes accentuated markedly. These data demonstrate that, in situations requiring high flow, the endocardial layer of a heart with marked concentric left ventricular hypertrophy may not be perfused adequately.     

The relationship between regional myocardial perfusion at rest and arteriographic lesions in patients with coronary atherosclerosis.

Measurements of mean left ventricular (LV) and regional myocardial blood flow rates were made at rest in 161 patients with 133Xe and a multiplecrystal scintillation camera. Myocardial perfusion rates were correlated with assessments of the degree of coronary artery disease made from the arteriograms obtained during the same studies. In patients with normal coronary arteries without heart failure, the presence of hypertension, aortic stenosis, or aortic insufficiency was not associated with changes in mean LV perfusion from the control value of 61+/-7 ml/100 g-min. However, mean LV perfusion was significantly reduced in patients with normal coronary arteries who had cariomyopathy and impaired ventricular performance. Mean LV perfusion was not significantly different from control values in patients with "mild" coronary artery disease (less than 50% obstruction) or in patients with significant isolated disease (greater than 50% obstruction) of the left anterior descending (lad) artery. Significant reductions in mean LV perfusion were found in patients with greater than 50% obstruction of two coronary arteries (LAD + right or LAD + circumflex) and in patients with triple-vessel disease. The average perfusion rate for regions distal to LAD obstructions in patients with isolated LAD disease was not lower than the LAD perfusion in control patients, but was significantly reduced in patients with LAD + right coronary artery disease (43+/-14 ml/100 g-min). In the latter group average perfusion distal to the LAD lesion was significantly lower than the average regional perfusion rate for the remainder of the LV. However, the mean blood flow rate for the remainder of the LV was also significantly lower than control values despite the lack of significant circumflex disease. The data demonstrate that the presence of radiographically "mild" or significant isolated LAD coronary disease is not associated with reductions in mean LV perfusion at rest, but that mean LV perfusion is reduced in the presence of significant disease of two or three coronary artieries. None of the patients experienced angina during the resting studies and most had clinical evidence of ventricular failure. The observation of depressed LV perfusion in this group, as in the patients with cardiomyopathy, raises the possibility that a lowered resting blood supply may be adequate for a reduced level of performance of a diseased ventricle. The lack of selective reductions of regional perfusion at rest in the majority of the patients with LAD lesions suggests that regional myocardial blood flow must be measured during an intervention which increases myocardial oxygen consumption in order to assess the physiological significance of lesions which are observed at coronary arteriography.     

Nitroglycerin and Heterogeneity of Myocardial Blood Flow REDUCED SUBENDOCARDIAL BLOOD FLOW AND VENTRICULAR CONTRACTILE FORCE

The effects of both intracoronary and intravenous administration of nitroglycerin on transmural distribution of blood flow in the left ventricle after partial coronary artery occlusion was investigated using two independent methods. In 16 open chest, anesthetized dogs, tubing supplying the cannulated left coronary artery was partially occluded. Strain gauges sutured paralled to superficial and deep fibers of the myocardium separately recorded the contractile force of each layer. With occlusion set so that depression of the deep contractile force was imminent. 12 mug intracoronary nitroglycerin in seven dogs depressed only the deep contractile force without changing systemic hemodynamics. Intravenous administration of 180 mug nitroglycerin in nine dogs resulted in a decrease of deep contractile force and aortic pressure often associated with an increase in superficial contractile force. Distribution of myocardial blood flow during peak coronary flow after intracoronary administration of nitroglycerin or during a decrease in aortic pressure after intravenous nitroglycerin administration was determined by the tissue uptake of an intracoronary bolus of rubidium-(80). This was compared with the uptake of potassium-(42) injected before nitroglycerin. Intravenous or intracoronary administration of nitroglycerin caused a significant reduction in subendocardial blood flow with a decrease in the subendocardial/subepicardial ratio of isotope.These experiments suggest that under conditions of acute partial coronary occlusion, the autoregulatory response results in more fully dilated subendocardial vessels causing them to be less responsive to nitroglycerin. Nitroglycerin may then reduce the vascular resistance in the subepicardial more than the subendocardial vessels, resulting in a "steal" of blood flow from deep to superficial myocardium.     

Correlation of contractile dysfunction with oxidative energy production and tissue high energy phosphate stores during partial coronary flow disruption in rabbit heart.

The relationships between contractile function, myocardial oxygen consumption, and tissue high energy phosphate and lactate content were investigated during partial coronary flow disruption. The experimental preparation was an isolated, isovolumic retrograde blood-perfused rabbit heart. Both developed pressure (r = 0.94) and dp/dt (r = 0.95) exhibited strong linear correlations with myocardial oxygen consumption that were stable for up to 45 min after blood flow reduction. In contrast, tissue high energy phosphate content exhibited nonlinear relationships with both developed pressure and oxygen consumption such that systolic mechanical function and oxidative metabolism declined to 20 and 30% of control values, respectively, before significant abnormalities in myocardial high energy phosphate stores were observed. Similarly, developed pressure and oxygen consumption decreased to 36 and 48% of control, respectively, before abnormal tissue lactate content was detected. The results of this study indicate that: (a) mechanical function is closely related to the rate of oxidative energy production during partial coronary flow disruption, and (b) despite the development of significant contractile dysfunction, tissue high energy phosphate content remains at normal levels except under the most severely flow-deprived conditions. The preservation of tissue energy stores can be explained by the apparent coupling of contractile performance to oxidative energy production, which could function to maintain myocardial energy balance during partial coronary flow restriction.     

The effects of glyceryl trinitrate,isosorbide dinitrate and sodium nitroprusside on haemodynamics,coronary blood flow and myocardial oxygen consumption — An experimental study

The influences of glyceryl trinitrate, isosorbide dinitrate and sodium nitroprusside intravenously on haemodynamics, coronary circulation and myocardial oxygen consumption were investigated in closed chest dogs (n=8). In an attempt to simulate heart failure the dogs received blood transfusion (15 ml/kg) in the presence of halothane-induced myocardial depression. All three nitrates reduced the loads for the left ventricle. With isosorbide dinitrate and sodium nitroprusside the preload and pulmonary pressure decreased to a greater extent than with glyceryl trinitrate. The haemodynamic results suggest that sodium nitroprusside is the favourable nitrate in left ventricular failure because it produces a balanced reduction in the ratio of pre- and afterload. Four μg/kg·min sodium nitroprusside induced marked coronary dilatation; glyceryl trinitrate had only a slight coronary vasodilating effect. With isosorbide dinitrate the myocardial blood flow remained well adapted to oxygen demand, the coronary vascular resistance did not change. Sodium nitroprusside produced a significant change of the transmural myocardial blood distribution-expressed as the epi/endocardial blood flow ratio. The ratio was increased by sodium nitroprusside, much more than by glyceryl trinitrate or isosorbide dinitrate.     

Echocardiographic diagnosis of the aorto-left ventricular tunnel

AIM/METHOD: The aorto-left ventricular tunnel (ALVT) is a rare congenital cardiac malformation with clinical findings of severe aortic insufficiency. We report the echocardiographic differentiation of different anatomical variants of ALVT in two infants. RESULTS: Echocardiography in both patients demonstrated severe enlargement of the ascending aorta and the left ventricle. In the first patient the ALVT originated from the ascending aorta above the right coronary sinus and entered the left ventricle just below the aortic valve. In the second patient the ALVT originated above the left coronary sinus and took a lateral course to the left ventricle. Colour-Doppler-sonography in both patients confirmed a systolic-diastolic flow across the tunnel. Many patients have associated cardiac defects. Exact determination of the morphology of the aortic valve and coronary arteries is mandatory for surgical repair. Postoperative follow-up studies focus on the function of the aortic valve and the left ventricle. CONCLUSION: Differentiation of different anatomical variants of ALVT is possible trough echocardiography. Cardiac catheterization is required only in cases with inadequate information about coronary artery anatomy.     

Effects of Increasing Heart Rate Induced by Efferent Sympathetic Neuronal Stimulation, Isoproterenol or Cardiac Pacing on Myocardial Function and Oxygen Utilization

The effects of increasing heart rate by six different methods on cardiac /unction were investigated in 17 open-chest anesthetized dogs. Heart rate was increased approximately 30% by (1) right interganglionic nerve stimulation, (2) atrial pacing, (3) ventricular pacing, (4) atriovenfricular sequential pacing, (5) right stellate ganglion stimulntion, and (6) isoproterenoi administration. During heart rate increases induced by atrial pacing left ventricular intramyocardial pressure, coronary Wood flow, oxygen delivery per unit of myocardial oxygen consumption, and myocardial efficiency were unchanged. Ventricular pacing reduced left ventricular cavity and septal intramyocardial pressure, while circumflex coronary flow increased, resulting in reduced oxygen delivery relative to myocardial oxygen consumption. Similarly, atrioventricu-lar sequential pacing increased circumflex coronary artery flow and myocardial oxygen consumption, and decreased septal intramyocardial pressure and oxygen delivery per unit of myocardial oxygen consumption. Right stellate ganglion stimulation and isoproterenol increased left anterior descending and circumflex coronary artery blood flow, intramyocardial pressure, and myocardial oxygen consumption. Estimated myocardial efficiency (left ventricle) was decreased by ventricular pacing and isoproterenol, and was unchanged by atrial pacing and right interganglionic nerve stimulation. Increases in heart rate induced by right interganglionic nerve stimulation did not alter myocardial oxygen consumption, or the index of cardiac efficiency. It is concluded that augmentation of heart rate by either ventricular or atrioventricular pacing impairs myocardial function so that there is a decrease of left ventricular efficiency, and isoproterenol augments chronotropism and myocardial force relative to cardiac external work so there is a reduction in cardiac efficiency. In contrast, atrial pacing or right interganglionic nerve stimulation augments chronotropism such that myocardial oxygen consumption and efficiency are unchanged.     

The effects of intra-aortic counterpulsation on cardiac performance and metabolism in shock associated with acute myocardial infarction

The effect of intra-aortic counterpulsation (IACP, 22-94 hr) on hemodynamics and cardiac energetics was evaluated in 10 patients in shock after acute myocardial infarction. The data clearly indicate that IACP improves myocardial oxygenation, enhances peripheral perfusion, and probably improves myocardial contractility in the severely diseased heart.Before treatment, decreases in cardiac index (mean value, 1.22 liter/min per m(2)), systolic ejection rate (67 ml/sec), and time-tension index per minute (1280 mm Hg.sec/min) were observed. Systemic vascular resistance varied widely. Low coronary blood flow (68 ml/min per 100 g) was associated with increased myocardial oxygen extraction (79%), low coronary sinus oxygen tension (20 mm Hg), and abnormal myocardial lactate-pyruvate metabolism.During 4-6 hr of IACP, systolic pressure and left ventricular outflow resistance decreased by 18% and 24%, respectively, while cardiac index improved by 38%. Diastolic arterial pressure rose 98%. Increase in coronary blood flow from an average of 68 to 91 ml/100 g per min (P < 0.001) was significantly correlated with rise in mean arterial pressure (r = 0.685). This correlation was best expressed in a third-order curve, which intercepts the point of no flow at a mean aortic pressure of 30 mm Hg. The flow-pressure curve is relatively flat above 65-70 mm Hg, but becomes steeper as mean aortic pressure falls below this point. Myocardial oxygen consumption remained essentially unchanged during early IACP and tended to rise during the later stages. However, the relationship of cardiac work performed to oxygen availability was markedly improved. Myocardial lactate production of 6% shifted to 15% extraction (P < 0.001).After termination of IACP, hemodynamics and myocardial perfusion and metabolism remained improved in the four patients who could be reevaluated. Although the acute shock state was reversed in all patients, only one left the hospital. Extensive myocardial damage limits the long-term survival of such patients. Therefore early IACP seems desirable, when subtle evidence of pump failure after acute myocardial infarction occurs. Early use of IACP may prevent the development of severe coronary shock or may stabilize cardiac energetics in severe shock facilitating subsequent surgical intervention.     

Evaluation of Bi-ventricular Coronary Flow Patterns Using High-Frequency Ultrasound in Mice with Transverse Aortic Constriction

Using high-frequency color and pulsed Doppler ultrasound, we evaluated the flow patterns of the left (LCA), septal (SCA) and right (RCA) coronary arteries in mice with and without transverse aortic constriction (TAC). Fifty-two male C57BL/6J mice were subjected to TAC or a corresponding sham operation. At 2 and 8 wk post-surgery, Doppler flow spectra from the three coronary arteries, together with morphologic and functional parameters of the left and right ventricles, were measured. Histology was performed to evaluate myocyte size and neo-angiogenesis in both ventricles. In sham-operated mice, the LCA and SCA both exhibited low-flow waveforms during systole and dominantly higher-flow waveforms during diastole. The RCA exhibited generally lower flow velocity, with similar systolic and diastolic waveforms. TAC significantly increased the systolic flow velocities of all coronary arteries, but enhanced the flow mainly in the LCA and SCA. In the left ventricle, coronary flow reserve was partially preserved 2 wk post-TAC, but decreased at 8 wk, consistent with changes in neo-angiogenesis and systolic function. In contrast, no significant change was found in the coronary flow reserve, structure or function of the right ventricle. This study has established a protocol for evaluating the flow pattern in three principal coronary arteries in mice using Doppler ultrasound and illustrated the difference among three vessels at baseline. In mice with TAC, the difference in the associating pattern of coronary flow dynamics with the myocardial structure and function between the left and right ventricles provides further insights into ventricular remodeling under pressure overload.     

4D flow心脏MRI测量左心室血流动力学参数的可靠性

目的 观察基于心脏MRI（CMRI）以局部区域性4D flow及全心4D flow技术测量左心室血流动力学参数的可靠性。方法 前瞻性对31名健康体健者采用心脏超声、三腔心4D flow（基于左心室流入流出道层面）及全心4D flow CMRI测量左心室血流动力学参数,以组内相关系数（ICC）评估其所测左心室血流动力学参数的一致性。结果 心脏超声与三腔心4D flow CMRI所测收缩期主动脉瓣上/瓣下峰值流速、舒张期二尖瓣E峰流速、主动脉瓣上/瓣下压力及主动脉瓣跨瓣压差的一致性均良好（ICC均>0.75）,所测舒张期二尖瓣A峰流速的一致性中等（ICC为0.718）;心脏超声与全心4D flow CMRI所测收缩期主动脉瓣上/瓣下峰值流速、舒张期二尖瓣A峰流速及主动脉瓣上/瓣下压力的一致性均良好（ICC均>0.75）,所测舒张期二尖瓣E峰流速及主动脉瓣跨瓣压差的一致性均为中等（ICC分别为0.600及0.628）;三腔心4D flow CMRI与全心4D flow CMRI测量上述指标结果的一致性均良好（ICC均>0.75）。结论 基于CMRI以局部区域性4D flow与全心4D flow技术测量左心室血流动力学参数可靠,与心脏超声测量结果具有良好一致性。     

Hemodynamics, coronary blood flow, and myocardial metabolism in coronary shock; response to l-norepinephrine and isoproterenol

Hemodynamics and myocardial metabolism were evaluated in 18 patients in cardiogenic shock following acute myocardial infarction. The response to l-norepinephrine was studied in seven cases and the response to isoproterenol in four cases. Cardiac index (CI) was markedly reduced, averaging 1.35 liters/min per m(2). Mean arterial pressure ranged from 40 to 65 mm Hg while systemic vascular resistance varied widely, averaging 1575 dyne-sec-cm(-5). Coronary blood flow (CBF) was decreased in all but three patients (range 60-95, mean 71 ml/100 g per min). Myocardial oxygen consumption (MV(O2)) was normal or increased ranging from 5.96 to 11.37 ml/100 g per min. Myocardial oxygen extraction was above 70% and coronary sinus oxygen tension was below 22 mm Hg in most of the patients. The detection of the abnormal oxygen pattern in spite of sampling of mixed coronary venous blood indicates the severity of myocardial hypoxia. In 15 studies myocardial lactate production was demonstrated; in the remaining three lactate extraction was below 10%. Excess lactate was present in 12 patients. During l-norepinephrine infusion CI increased insignificantly. Increased arterial pressure was associated in all patients by increases in CBF, averaging 28% (P < 0.01). Myocardial metabolism improved. Increases in MV(O2) mainly paralled increases in CBF. Myocardial lactate production shifted to extraction in three patients and extraction improved in three. During isoproterenol infusion CI increased uniformly, averaging 61%. Mean arterial pressure remained unchanged but diastolic arterial pressure fell. CBF increased in three patients, secondary to decrease in CVR. Myocardial lactate metabolism deteriorated uniformly; lactate production increased or extraction shifted to production. In the acute state of coronary shock the primary therapeutic concern should be directed towards the myocardium and not towards peripheral circulation. Since forward and collateral flow through the severely diseased coronary bed depends mainly on perfusion pressure, l-norepinephrine appears to be superior to isoproterenol; phase-shift balloon pumping may be considered early when pharmacologic therapy is unsuccessful.     

Systemic and coronary hemodynamic actions of the novel inotropic agent, ibopamine, and the de-esterified metabolite and active form, epinine: relationship to left ventricular performance in the dog

The relationship between the systemic hemodynamic, inotropic and coronary blood flow actions of the novel inotropic pro-drug, ibopamine, which is the 3,4-diisobutyryl ester derivative of the active form, epinine, was examined in pentobarbital-anesthetized, vagotomized dogs prepared for the recording of systemic arterial blood pressure, heart rate, left ventricular developed pressure and end-diastolic pressure, left ventricular dP/dt, aortic blood flow, left circumflex coronary artery blood flow and lead II ECG. All animals were given i.v. infusions of vehicle followed by 10 min infusions of either epinine (1.1, 3.3, 10 and 30 micrograms/kg/min, n = 4) or ibopamine (3.3, 10, 30 and 100 micrograms/kg/min, n = 4). Both epinine and ibopamine produced dose-dependent increases in mean arterial blood pressure, heart rate, left ventricular developed pressure, left ventricular dP/dt, aortic blood flow, coronary blood flow, left ventricular minute work, stroke work, total peripheral vascular resistance and rate-pressure product. Both epinine and ibopamine decreased coronary vascular resistance, although only the decrease produced by ibopamine achieved statistical significance (P less than .05). Examination of the dose-response curves for epinine and ibopamine showed epinine to be 3- to 4-fold more potent than ibopamine with respect to increasing coronary blood flow, left ventricular stroke work, left ventricular dP/dt and rate-pressure product. However, neither drug increased myocardial work, myocardial oxygen consumption or contractility to a greater extent than the increase in coronary blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regional Myocardial Perfusion Rates in Patients with Coronary Artery Disease

Regional myocardial perfusion rates were estimated from the myocardial washout of (133)Xenon in 24 patients with heart disease whose coronary arteriograms were abnormal and 17 similar subjects whose coronary arteriograms were judged to be normal. Disappearance rates of (133)Xe from multiple areas of the heart were monitored externally with a multiple-crystal scintillation camera after the isotope had been injected into a coronary artery and local myocardial perfusion rates were calculated by the Kety formula.The mean myocardial perfusion rates in the left ventricle exceeded those in the right ventricle or atrial regions in subjects without demonstrable coronary artery disease. In this group there was a significant lack of homogeneity of local perfusion rates in left ventricular myocardium; the mean coefficient of variation of left ventricular local perfusion rates was 15.8%.In the patients with radiographically demonstrable coronary artery disease, a variety of myocardial perfusion patterns were observed. Local capillary blood flow rates were depressed throughout the myocardium of patients with diffuse coronary disease but were subnormal only in discrete myocardial regions of others with localized occlusive disease. Local myocardial perfusion rates were similar to those found in the group with normal coronary arteriograms in patients with slight degrees of coronary disease and in those areas of myocardium distal to marked coronary constrictions or occlusions which were well supplied by collateral vessels.In subjects with right coronary disease, the mean right ventricular perfusion rates were significantly subnormal; in seven subjects of this group perfusion of the inferior left ventricle by a dominant right coronary artery was absent or depressed. The average mean left ventricular perfusion rate of 12 subjects with significant disease of two or more branches of the left coronary artery was significantly lower than that of the group with normal left coronary arteriograms. In the patients with abnormal left coronary arteriograms, the average coefficient of variation of local left ventricular perfusion rates was significantly increased (24.8%).The studies provide evidence that coronary artery disease is associated with increased heterogeneity of local myocardial perfusion rates. They indicate that radiographically significant vascular pathology of the right or left coronary artery may be associated with significant reductions of myocardial capillary perfusion in the region supplied by the diseased vessel.     

Hemodynamic effects of aortic valve and heart rate on coronary perfusion

BackgroundReduced coronary flow reserve in aortic stenosis and after transcatheter aortic valve implantation is usually attributed to physiological factors taking place during systole, such as an increase in coronary resistance, and backward waves intensity. In this paper, we suggest an additional factor related to the diastolic hemodynamics in the aortic root.MethodsWe measured left ventricle, aortic and coronary pressure and coronary perfusion in in-vitro models of healthy, aortic stenosis and an artificial valve at different heart rates and cardiac output conditions, to isolate the effect of hemodynamic factors in the aortic root during diastole.FindingsOur results show that during diastole, coronary perfusion depends on the pressure gradient between the aorta and the coronary inlet. This aorta-coronary pressure gradient is influenced by the hemodynamic flow field in the aortic root. The ratio between the aorta-coronary pressure gradient magnitude in stress to that under rest conditions of a healthy model is ten times higher than the same ratio in the aortic stenosis model and twice higher as compared to the artificial valve model result. The coronary flow reserve of the healthy model is correspondingly higher compared to the artificial valve and the aortic stenosis models. These results are in agreement with the clinical evidence.InterpretationThis study supports the hypothesis of a hemodynamic mechanism in the aortic root that increases coronary flow during rest but reduces the coronary flow reserve in aortic stenosis and artificial valve cases. The results may provide valuable insights regarding valve design.