Capillary perfusion in the occluded-reperfused canine myocardium: evidence for slowed reflow.

The purpose of this study was to determine if the no-reflow phenomenon in the occluded/reperfused dog heart was anatomical (capillary bed could not be perfused) or functional (slowed capillary perfusion). The left anterior descending (LAD) coronary artery was isolated in anesthetized open-chest dogs. The LAD was occluded (2 hr) then reperfused (4 hr). A total of 14 dogs were assigned to one of two groups: The multiple pass (MP) or single pass (SP) group. Fluorescent labeled dextran (FITC) was injected and circulated either for 10 min in the MP group or for one pass of the circulation in the SP group. In the last 2 min, the MP group was asphyxiated. Hearts were excised and frozen in liquid nitrogen. The LAD and control region were isolated and frozen sections (5 microns) obtained. Sections were photographed under fluorescent light and then immunohistochemically stained. The microvessels were identified by visualizing the endothelium with a Factor VIII antibody. The specific areas photographed were relocated. The total number of capillaries, determined by stain outlining a lumen of no greater than 10 microns in diameter, were counted. This number was compared to the number of microvessels containing FITC-dextran. There was no difference in the total perfusable capillary bed in the MP group between the control and LAD regions (80 +/- 4 and 82 +/- 10%). In the SP group, there was a significant difference between the control and LAD regions (59 +/- 25 and 46 +/- 14%). The percentage of the capillary bed perfused in the SP group was less than the MP group in each region. Closest individual analysis of the perfused capillary distribution in the SP group, showed the distribution in the LAD region was random, potentially clustered and more dispersed compared to the control region. This study provides data against physical obstruction of the capillary bed secondary to ischemia. The data suggest sluggish and clustered perfusion in the occluded-reperfused myocardium during a single pass of the coronary circulation.

Reduction of cardiac hypertrophy in renal hypertensive rabbits with pindolol.

Arterial pressure, cardiac mass and coronary flow reserves were measured in untreated and chronically pindolol-treated rabbits, prepared as either one-kidney one clip (1K1C) hypertensive or uninephrectomized (sham) controls. Pindolol (200 micrograms/kg/day) was administered for either 23 or 30 days, beginning 1 week after, or the day of initial surgery, respectively. Coronary flow was measured, at day 30, using radioactive microspheres, during base-line and adenosine infusion (0.4 mg/kg/min) in anesthetized open-chest preparations. Heart weight of untreated 1K1C animals (9.13 +/- 0.73 g) was significantly greater than the controls (7.19 +/- 0.77 g). Myocardial mass of 1K1C (9.93 +/- 0.86 g) and sham controls (7.40 +/- 0.31 g) were unaffected by chronic pindolol for 23 days. Cardiac hypertrophy was prevented in 1K1C animals treated with pindolol for 30 days (7.53 +/- 1.28 g). Untreated 1K1C animals were hypertensive compared to sham controls (116 +/- 12 and 78 +/- 7 mm Hg) and neither pindolol regime affected blood pressure. Bradycardia was evident in all pindolol-treated animals. Base-line coronary flow was higher in the untreated 1K1C animals compared to untreated controls (228 +/- 43 vs. 182 +/- 31 ml/min/100 g). After chronic pindolol treatments, 1K1C base-line blood flows were reduced (158 +/- 48 and 175 +/- 59 ml/min/100 g, for 23- and 30-day protocols). Adenosine vasodilated flows were not different between the untreated 1K1C and sham animals and were not affected by pindolol treatment. Therefore, hypertension and cardiac hypertrophy were dissociable in this model when pindolol was administered from the onset of hypertension. This suggests immediate involvement of beta adrenergic activation in the development of hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

Isoproterenol and myocardial O2 supply/consumption in hypertension-induced myocardial hypertrophy.

Myocardial oxygen supply, O2 consumption (MVO2) and function were determined during base-line and isoproterenol infusion (0.5 microgram.kg-1.min-1) 30 days after New Zealand White rabbits were prepared as one-kidney, one-clip (1K,1C) Goldblatt hypertensive or uninephrectomized (sham) controls. Coronary blood flow and cardiac output, using radioactive microspheres, and small vessel O2 saturations, using microspectrophotometry, were measured in hypertrophied and nonhypertrophied hearts. After 30 days, 33% myocardial hypertrophy was evident in the 1K,1C animals. Base-line blood pressure was significantly higher in the 1K,1C animals compared with sham controls and remained higher during isoproterenol infusion. Base-line heart rate was not different between animal groups, and heart rate increased in both groups during isoproterenol. Cardiac output was similar between sham and 1K,1C animals during base-line conditions (316 +/- 40 vs. 365 +/- 51 ml/min, respectively). After isoproterenol, cardiac output increased in the sham animals (494 +/- 119 ml/min) but not in the 1K,1C group (317 +/- 85 ml/min). Isoproterenol elevated MVO2 threefold in both the sham and 1K,1C animals. Coronary blood flow was significantly increased to similar levels in both animal groups. O2 extraction significantly increased during isoproterenol in both groups. Therefore, impaired cardiac function was evident during isoproterenol stress in the hypertrophied myocardium independent of myocardial O2 supply or consumption restrictions.

Hypertension-induced cardiac hypertrophy. Oxygen supply and consumption with pacing.

The purpose of this study was to determine if hypertrophied myocardium was associated with diminished cardiac function, restricted oxygen supply, or oxygen consumption during tachycardia. Myocardial oxygen supply and oxygen consumption were determined during baseline and atrial pacing conditions 30 days after New Zealand White rabbits were prepared as one-kidney, one clip Goldblatt hypertensive or uninephrectomized sham control rabbits. Coronary blood flow and cardiac output, using radioactive microspheres, and small vessel oxygen saturations, using microspectrophotometry, were measured in hypertrophied and nonhypertrophied hearts. After 30 days, baseline blood pressure was significantly higher in the Goldblatt rabbits compared with sham controls, and hypertension was maintained during pacing. The myocardium was hypertrophied in the Goldblatt hypertensive rabbits compared with sham controls. Baseline heart rates were not different between animal groups (242 +/- 32 and 244 +/- 24 beats/min, respectively). Both groups were paced 35% above baseline heart rates; during pacing, cardiac output was similar to baseline values in the sham controls (304 +/- 99 versus 321 +/- 116 ml/min, respectively) but reduced in the hypertensive rabbits (248 +/- 43 versus 325 +/- 62 ml/min). Myocardial oxygen consumption increased twofold in both nonhypertrophied and hypertrophied ventricles during tachycardia. Oxygen extraction was significantly elevated, but coronary blood flow was not altered during pacing in either animal group. Therefore, at the pacing level chosen the diminished function in cardiac hypertrophy was not associated with reduced oxygen consumption. Conversely, reduced efficiency during pacing in the hypertrophied myocardium was suggested.

Microvascular perfusion during atrial pacing in renal hypertension induced cardiac hypertrophy.

The purpose of this study was to determine if microvascular reserve was recruited during atrial pacing in the hypertrophied myocardium. Hypertrophy was induced by one-kidney, one-clip (1K1C) renal hypertension and compared to uninephrectomized control rabbits 30 days after surgery. Coronary flow was determined by radioactive microspheres. Microvascular perfusion was determined by comparison of fluorescein isothiocyanate-dextran labeled vessels with an alkaline phosphatase stain. Heart rates were not different between groups and all animals were paced 35% above baseline. Baseline coronary flow (176 +/- 44 and 207 +/- 61 ml/min/100 g, control and 1K1C animals) was not altered by pacing in either group. The baseline percent of capillaries perfused was not different between groups (56 +/- 2 and 61 +/- 3%, sham and 1K1C) and the percent perfused increased significantly during pacing for both the non-hypertrophied and 1K1C myocardium (76 +/- 6 and 78 +/- 10%). The baseline percent of the arteriolar bed perfused, was higher in the 1K1C (86 +/- 5%) compared to non-hypertrophied (63 +/- 6%) myocardium. During pacing, the percent of the arteriolar bed perfused increased in non-hypertrophied (89 +/- 14%) but not in the 1K1C myocardium. Although the percent of arterioles perfused did not increase with pacing in the 1K1C myocardium, the capillary reserve was recruited, facilitating the transport of O2 in both the hypertrophied and non-hypertrophied myocardium.

Myocardial O2 supply and consumption in early cardiac hypertrophy of renal hypertensive rabbits.

This study examined myocardial O2 supply and O2 consumption in hypertension-induced myocardial hypertrophy. New Zealand white rabbits prepared as uninephrectomized (sham) controls (n = 7), or one kidney/one clip (1K1C) hypertensive rabbits (n = 7) were examined four weeks after surgery. A group of renally intact "true" controls (n = 4) was also examined. Coronary blood flow (CBF) was measured with radioactive microspheres in anesthetized open chest animals during baseline and vasodilated conditions (adenosine, 0.4 mg/kg/min). Microvascular O2 saturations were determined by microspectrophotometry. Myocardial oxygen consumption (MVO2) was calculated. Mean pressure was elevated in hypertensive animals (121 +/- 7 mmHg, means +/- SE) compared to uninephrectomized controls (74 +/- 7 mmHg). Hypertrophy was indicated by a 30% increase in heart weight to body weight ratio in the 1K1C animals. The average MVO2 was elevated in hypertrophy (12.4 +/- 0.9 vs. 9.6 +/- 0.8 ml O2/min/100 g). Baseline CBF was higher in cardiac hypertrophy (227 +/- 21 ml/min/100 g) compared to sham controls (169 +/- 14 ml/min/100 g). In hypertrophy the percent increase in CBF during adenosine infusion was reduced and the minimal vascular resistance was higher. No difference in microvascular O2 saturations was observed between groups, thus O2 extraction was similar. No subepicardial vs. subendocardial difference occurred within either the sham controls or the 1K1C animals in any parameter. Therefore, an overall increased MVO2 resulted in increased CBF and reduced coronary flow reserve in short-term renovascular hypertension-induced cardiac hypertrophy in rabbits.

Microvascular morphometry and perfusion in renal hypertension-induced cardiac hypertrophy.

This study examined alterations in microvascular morphometry and perfusion occurring concomitantly with changes in coronary blood flow (CBF), flow reserves, and coronary vascular resistance (CVR) in myocardial hypertrophy. New Zealand White rabbits (n = 28) with one-kidney, one-clip hypertension (1K,1C) or uninephrectomy (control) were examined 4 wk after surgery in anesthetized open-chest preparations. Animals were divided into two experimental series. In the first series, flows were determined with radioactive microspheres during rest and adenosine-induced vasodilation. In a second series, fluorescein isothiocyanate dextran (FITC-dextran) was injected to visualize the perfused arteriolar and capillary beds. The total vasculature was marked with an alkaline phosphatase stain. Mean arterial pressure was elevated in 1K,1C animals (110 +/- 7 mmHg, means +/- SE) when compared with controls (77 + 4 mmHg), and the myocardial weight was greater. Resting CBF was higher in 1K,1C animals compared with controls (227 +/- 21 vs. 168 +/- 12 ml.min-1.100 g-1), and the flow reserve was reduced. Minimal CVR was higher in 1K,1C compared with controls (0.190 +/- 0.035 vs. 0.091 +/- 0.018 mmHg.ml-1.min.100 g). The number of capillaries per squared millimeter was not different from control (2,448 + 121 vs. 2,216 +/- 132/mm2) and the percent perfused was similar (56 +/- 2 vs. 61 +/- 3%). The arteriolar density in cardiac hypertrophy was lower (1.2 +/- 0.2 vs. 2.1 +/- 0.3/mm2), and the percent perfused was higher (86 +/- 5 vs. 63 + 6%) compared with controls. Thus, in myocardial hypertrophy, the anatomical density and volume fraction of arterioles appears to be reduced, and the percentage of arterioles perfused increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Non-invasive blood pressure measurement in Yucatan miniature swine using tail cuff sphygmomanometry.

A relatively new non-invasive method using a photo-electric flow sensor in non-heated animals, was evaluated for its accuracy in measuring systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) in 40-90 Kg normotensive and hypertensive Yucatan miniature swine. Directly measured SBP, DBP and electronically averaged MAP were recorded from chronic arterial catheters simultaneously with indirect pressures, cuff pressure and tail blood flow under various conditions. In all of the tests tail cuff SBP estimation averaged within 5% of directly measured SBP. The correlation of the two methods was significant (r = .95, P less than 0.01). Over a 60 to 202 mmHg range of blood pressure induced pharmacologically or due to DOCA hypertension, the tail cuff SBP was within 4-10% of directly measured SBP. The tail cuff method was also used to determine DBP and MAP. DBP determined from the tail cuff record was found consistently to underestimate the direct measured DBP by approximately 17%. The two methods were correlated (r = .87 P less than 0.01). The measured tail cuff MAP generally underestimated the direct MAP by approximately 5%. The correlation of directly measured MAP and tail cuff methods was significant (r = .72, P less than 0.01). These results indicated that this system may be used to accurately assess blood pressure in miniature swine.

Adrenocortical function in deoxycorticosterone acetate (DOCA)-hypertensive Yucatan miniature swine.

Adrenocortical function was assessed in six normal and six chronic (greater than 12 weeks), DOCA-hypertensive Yucatan miniature swine; mean arterial pressures were 115.3 +/- 11.7 and 163.6 +/- 27.2 mm Hg, respectively (mean +/- SEM). Adrenocortical function was evaluated in vivo by measuring changes in plasma cortisol and aldosterone in response to exogenous ACTH (0.25 mg, iv), and in vitro by measuring the responses of collagenase-isolated adrenocortical cells to ACTH and angiotensin II. Corticoids were measured by specific radioimmunoassay. Basal plasma cortisol values of conscious DOCA-hypertensive swine were approximately 53% of the values of normotensive swine (P less than 0.05). However, ACTH induced a 419% increase in plasma cortisol values in DOCA-hypertensive swine compared to a 261% increase in the normotensive swine (P less than 0.05). These differences between the two groups were not altered by anesthesia. There were no significant differences in ACTH-induced changes in plasma aldosterone between the normotensive and DOCA-hypertensive swine. Experiments in vitro showed that the corticoid secretory responses of adrenocortical cells from DOCA-hypertensive animals were 6 times more sensitive to ACTH and 3.2 times more sensitive to angiotensin II than those of cells from normotensive swine. Thus, despite the possibility of adrenocortical insufficiency due to suppressed plasma renin activity and the negative feedback of DOCA on the hypothalamic-hypophyseal-adrenal axis, adrenocortical function of DOCA-hypertensive swine was hyperresponsive to trophic hormones. Results from this study suggest that the DOCA-hypertensive swine may be a valuable model in elucidating the relationship between hypertension and adrenocortical function and in investigating nonclassical control of the adrenal cortex, that is, control exerted during the hypertensive state that exists apart from or in addition to that exerted by ACTH and angiotensin II.