Regional metabolic rate of exogenous glucose in the isoprenaline and dobutamine stimulated canine myocardium as estimated by the 2-deoxy-D[1-14C]glucose method.

The effect of beta-adrenoceptor stimulation by isoprenaline and dobutamine on the transmural distribution pattern of regional myocardial metabolic rate of exogenous glucose (RMMRGlc) was studied in the anesthetized closed chest dog using the 2-deoxy-D[1-14C]glucose method. In a previous series a lumped constant (LC) value of 0.93 +/- 0.47 (1 SD) was measured for [14C]2-deoxyglucose in the canine myocardium. In the control group (N = 12) RMMRGlc was significantly higher in the subendocardial layer of the left ventricular free wall than in both the middle and subepicardial layer, where it was quite evenly distributed (P less than or equal to 0.05). With i.v. dobutamine (N = 8) RMMRGlc was significantly lower in the midportion of left ventricular free wall than in the subepicardial layer (P less than or equal to 0.05), but it was not different from the inner wall section. Significant differences between the subepicardial and subendocardial portions of the left ventricular free wall could not be found, either. In the isoprenaline group (N = 9) no transmural gradients of RMMRGlc were observed in the left ventricular myocardium. In all groups, both the interventricular septum and the right ventricular free wall exhibited homogeneous distribution patterns of RMMRGlc. It is concluded that transmural distribution patterns of exogenous glucose utilization probably reflect corresponding gradients in energy demands of the left ventricular wall. Redistribution of RMMRGlc in the isoprenaline and dobutamine groups may result from altered working conditions, a change in local inotropic state of the left ventricular myocardium, or from regional differences in the proportions of substrate utilization, and from regional differences in adrenoceptor density.

Distribution of myocardial glucose consumption under normal conditions and during isoprenaline and dobutamine infusion.

The regional myocardial metabolic rate of glucose (reg. MMR Gl) of the left ventricular free wall was determined applying the 2-deoxyglucose method (Sokoloff, 1977) in the anesthetized closed chest dog. Under control conditions an inhomogeneous distribution of MMR Gl was observed. Isoprenaline or dobutamine infusions resulted in a redistribution of MMR Gl. With isoprenaline a homogeneous distribution pattern was observed, while with dobutamine a slight decrease in MMR Gl of the subendocardial region was measured. This redistribution may result from altered ventricular working conditions, due to changes in ventricular volumes or from differences in the frequency of myocardial adrenoceptors within the ventricular wall.

Regional glucose consumption and oxygen supply in the isolated perfused working rat heart.

Using 2-Deoxyglucose as a tracer, regional myocardial metabolic rate of glucose (MMR GL) has been determined in an isolated perfused working heart preparation. Under control conditions (n = 8) mean glucose consumption of the left ventricular wall amounted to 1.17 +/- 0.24 mumol X g-1 X min-1, which was about twice that of the right ventricular wall. There was an inhomogeneous distribution of MMR GL in the left ventricular wall with the endocardial rates exceeding the epicardial ones by about 20%. Isoprenaline (1.25 micrograms X L, n = 9) induced an increase in heart rate and a decrease in cardiac output. Under these conditions mean glucose consumption increased by about 20%, and a redistribution of MMR GL was observed in the left ventricular wall. As, in the preparation used, only glucose was offered as an exogeneous substrate, this redistribution should reflect a similar redistribution of myocardial energy metabolism and, therefore, muscular tension developed in the different layers of the ventricular wall.

Blood flow redistribution by dopamine in the feline gastrointestinal tract.

The effect of intravenous infusion of dopamine (10 and 25 micrograms X kg-1 X min-1 consecutively) on visceral blood flow distribution was examined in anesthetized cats using the microsphere technique and electromagnetic flowmetry. Arterial blood pressure did not change in response to dopamine infusion, but blood flow through the superior mesenteric artery, and blood flow in the mucosa-submucosa of the gastric antrum and various gut segments increased significantly. During infusion of the high dose the increase was most marked in the mucosa-submucosa of the antrum (+355%) and distal colon (+371%). By contrast, blood flow decreased in the muscularis-serosa of the gut segments investigated, in the spleen, pancreas, and the hepatic arterial bed. The increase in blood flow through the superior mesenteric artery was blocked by the dopamine antagonist bulbocapnine (10 mg/kg i.v.). The results suggest that the receptors mediating the dopamine-induced vasodilation in the gastrointestinal tract are located in the resistance vessels of the mucosa-submucosa.

Dopamine produces vasodilation in specific regions and layers of the rabbit gastrointestinal tract.

The effect of intravenous dopamine infusion (25 and 60 micrograms per kg and min consecutively) on blood flow distribution in the splanchnic region of anesthetized rabbits was studied applying the microsphere technique. During infusion of the low dose, blood flow increased most markedly in the stomach, less in the pancreas, jejunum and descending colon, and decreased in the spleen. In the stomach the increase was confined to the mucosa-submucosa. Raising the dose of dopamine resulted in a slight fall of arterial blood pressure, a further increase in blood flow through the mucosa-submucosa of the gastric fundus (+493 % as against control), but not through the other tissues studied. In another series, blood flow through the left gastric artery was measured with an electromagnetic flowmeter. The infusion of dopamine produced a dose-dependent increase in regional blood flow, which was inhibited by the dopamine antagonist bulbocapnine. Furthermore, the control blood flow was transiently decreased, and resistance to flow was increased by bulbocapnine. The results indicate that the dopamine-induced vasodilation in the gastrointestinal tract of the rabbit is largely restricted to the gastric circulation and suggest that specific receptors mediating this vasodilation are located in the mucosa-submucosa. It is hypothesized that endogenous dopamine functions as a vasodilatory tissue hormone in the gastric mucosa of the rabbit.

Transmural gradients in myocardial metabolic rate.

To examine the 2-deoxyglucose (2-DG)-method for myocardial tissue, glucose uptake was measured directly and via the 2-DG-technique in 16 isolated perfused guinea pig hearts. A correlation (r = 0.7; p less than 0.01) between both methods was found. In the in situ working canine heart 2-DG revealed a 20% higher glucose uptake of the subendocardial layers as compared with the subepicardial. Blood flow to these layers, estimated by albumin aggregates, exceeded that to the subepicardial by 82%. Thoracotomy resulted in a homogeneous distribution of blood flow and tissue PO2, comparable to a homogeneous distribution of glucose uptake in isolated perfused hearts.

Regional distribution of vascular resistance in two models of experimental renovascular hypertension.

The regional distribution of the peripheral vascular resistance was studied in normotensive and hypertensive Wistar rats. Two models of experimental hypertension were investigated: (I) in 32 animals the right renal artery was constricted by a silver clip (two-kidney Goldblatt hypertension); (II) in 46 animals the left kidney was removed and the right renal artery was clipped as in the first group (one-kidney Goldblatt hypertension). The normotensive control group comprised 61 untreated animals of the same strain and age. The distribution of cardiac output to 14 tissues was determined by means of the particle distribution technique. The resistance was increased in all regions investigated, a decreased or unchanged resistance was not observed. For most of the investigated tissues the regional resistance was increased exactly in proportion to the total peripheral resistance (TPR). Exceptions to this were found in 2 regions where the change of local resistance deviated from that of TPR: the splanchnic area and the skeletal muscle. In both cases the 2 models differed from each other. In the two-kidney model the increase of resistance in the splanchnic circulation was more intense than in other organs. In contrast, in the one-kidney model the local change of resistance was less than that of TPR. The change of skeletal muscle resistance was not significantly different from the change of TPR in the two-kidney model, while in the one-kidney model the increase of local resistance was significantly higher than that of TPR. It is concluded that the etiology of the abnormal resistance is different in the 2 models investigated and that known extrinsinc pressor factors may play a role in the two-kidney, but not in the one-kidney Goldblatt hypertension.

Effect of etafenone on total and regional myocardial blood flow.

The distribution of blood flow to the subendocardial, medium and subepicardial layers of the left ventricular free wall was studied in anaesthetized dogs under normoxic (A), hypoxic (B) conditions and under pharmacologically induced (etafenone) coronary vasodilation (C). Regional myocardial blood flow was determined by means of the particle distribution method. In normoxia a transmural gradient of flow was observed, with the subendocardial layers receiving a significantly higher flow rate compared with the subepicardial layers. In hypoxia induced vasodilation this transmural gradient of flow was persistent. In contrast a marked redistribution of regional flow was observed under pharmacologically induced vasodilation. The transmural gradient decreased. In contrast to some findings these experiments demonstrate that a considerable vasodilatory capacity exists in all layers of the myocardium and can be utilized by drugs. The differences observed for the intramural distribution pattern of flow under hypoxia and drug induced vasodilation support the hypothesis that this pattern reflects corresponding gradients of regional myocardial metabolism.