Regional oxygen supply and consumption balance in experimental left ventricular hypertrophy

Summary The aim of the present study was to determine if the relationship between myocardial O₂ supply and O₂ consumption was preserved after prolonged pressure overload due to aortic valve stenosis. This was examined in anesthetized open-chest dogs in which the aortic valve was plicated 6 months previously. We measured coronary blood flow with radioactive microspheres and regional small vessel O₂ saturation with microspectrophotometry, to obtain O₂ supply, and O₂ consumption. Regional O₂ consumption was calculated as the product of flow and O₂ extraction. The left ventricular weight/body weight ratio was 81% greater in the dogs with aortic valve stenosis. There were no hemodynamic differences between the groups except that left ventricular systolic pressure was 38±22 mm Hg greater than aortic in the hypertrophied group. Coronary blood flow did not differ between the control and hypertrophied groups nor were there subepicardial vs subendocardial differences. When maximal coronary flow was determined with chromonar (10 mg/kg), the flow increase was significantly attenuated in the hypertrophied subendocardium (242.1±82.3 (hypertrophy) vs 512.4±204.1 ml·min^–1·100 g^–1 (control)). There were no significant differences in O₂ extraction or O₂ consumption/g between control and hypertrophied animals. There was a significantly lower O₂ supply/consumption ratio in the subendocardium compared to the subepicardium of both groups. However, the O₂ supply/consumption ratio was not decreased by hypertrophy. Thus, despite significant hypertrophy, a loss of flow reserve and a high left ventricular pressure, O₂ supply/consumption balance is preserved in valvular aortic stenosis at rest.     

Effect of coronary hyperperfusion on regional myocardial function and oxygen consumption of stunned myocardium in pigs

Summary The Gregg phenomenon implies that myocardial function and oxygen consumption ( ) increase when coronary perfusion is enhanced within or above the autoregulatory range. We have recently demonstrated that the Gregg phenomenon has no significance for regional myocardial function and in anesthetized swine in situ. There is, however, some evidence that the Gregg phenomenon may exist within stunned myocardium. To test whether coronary hyperperfusion increases regional myocardial function and in stunned myocardium, in six anesthetized swine the left anterior descending coronary artery (LAD) was cannulated and perfused at constant pressure (CAP) using an extracorporal circuit. The coronary vein which parallels the LAD was cannulated to allow measurement of regional and regional systolic wall thickening (WT%) of the anterior myocardium was assessed using sonomicrometry. Blood flow (CBF) to the LAD was increased by increasing CAP within the extracorporal circuit or by intracoronary adenosine infusion (150 g/min). In normal myocardium, increasing CBF from 71.4 ± 19.7 (SD) to 156.7 ± 48.8 ml/min/100 g by increasing CAP from 100 ± 10 to 190 ± 10 mm Hg or increasing CBF from 75.1 ± 29.1 to 189.2 ± 45.8 ml/min/100 g by intracoronary adenosine infusion did not increase WT% (34.3 ± 12.2 % vs 32.1 ± 10.6 % and 32.3 ± 10.7 % vs 30.1 ± 13.2 %, respectively). was not changed during enhanced CAP (6.94 ± 1.05 vs 8.10 ± 1.08 ml/min/100 g) and during intracoronary adenosine infusion (6.67 ± 1.45 vs 7.30 ± 2.23 ml/min/100 g). Twenty min of hypoperfusion followed by 30 min of reperfusion depressed WT% by 47 % (p < 0.05). However, was only decreased by 23 % (NS). In the stunned myocardium, increasing CBF from 62.1 ± 36.4 to 157.1 ± 60.0 ml/min by increasing CAP was not associated with an increase in WT%. , however, increased from 5.14 ± 1.07 to 8.88 ± 1.83 ml/min/100 g (p < 0.05). Comparable results were achieved when CBF was increased from 60.3 ± 28.7 to 176.9 ± 48.5 ml/min by intracoronary adenosine infusion. WT% was unaffected, while increased from 4.69 ± 0.92 to 9.46 ± 3.39 ml/min/100 g (p < 0.05). Thus, increasing coronary perfusion within or above the autoregulatory range increases in stunned myocardium, but without a simultaneous increase in regional myocardial function.     

Evaluation of parameters for the assessment of regional myocardial contractile function during asynchronous left ventricular contraction

Summary The primary purpose of this study was to evaluate parameters used for the measurement of regional myocardial contractile function in the setting of left ventricular (LV) asynchrony. Secondarily, we tested whether the peak negative value of left ventricular dP/dt (-dP/dt) can be used to estimate global LV end-systole during asynchrony. In seven anesthetized (Isoflurane) swine the left anterior descending coronary artery was cannulated and perfused at constant blood flow rates. To produce LV asynchrony, dobutamine (D) was infused into the perfusion system. This was repcated later during coronary hypoperfusion (HYPO) sufficient to produce regional contractile dysfunction. The amount of LV wall thickening during systole (% WT, sonomicrometry) was calculated using either - dP/dt or the closure of the aortic valve (AO, electromagnctic flow probc) for estimating the timing of global LV end-systole. % WT was compared to other paramcters which are not dependent upon the timing of global LV end-systole, including the amplitude of the first harmonic of the Fourier transform (AMP) and regional myocardial work (WI) estimated from the left ventricular pressure-wall thickness relationship. A close correlation between global LV end-systole defined by the AO or - dP/dt existed during control. D or HYPO. During HYPO+D no such relationship was found (r=.22, NS), and % WT calculated using - dP/dt as an estimate of end-systole was underestimated when comparcd to % WT calculated by use of the AO to estimate end-systole (2.9±6.8% vs 6.3±6.6%, p<.05). % WT, AMP, and WI showed similar results during control, D and HYPO. However, D during HYPO increased the AMP from .59±.23 mm to .76±.32 mm and WI from 67±20 mm Hg*mm to 95±24 mm Hg*mm (p<.05), respectively. This increase in regional myocardial function, however, was not detected by % WT (10.5±6.4% vs 6.3±6.6%). Thus, during left ventricular asynchrony, the measurement of LV-dP/dt to estimate the timing of global LV end-systole is inappropriate and can lcad to inaccuracies in the measurement of regional contractile function. Parameters such as AMP or WI are advantageous since global LV end-systole docs not need to be accurately defined.Supported in part by the American Heart Association California Affiliate grant-in-aid #86-S105, and by the German Research Foundation (He 1320/3-2). Dr. Guth is the recipient of a Research Fellowship from the Alexander von Humboldt-Stiftung, Jean-Paul-Straße 12, D-5300 Bonn 2     

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

Summary 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 mm Hg, ) compared to uninephrectomized controls (74±7 mm Hg). 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.     

Changes in ECG,plasma and myocardial lipids in experimental myocardial hypertrophy in rats

Summary ECG, systolic blood pressure (BP), the ratio (R) of grams of myocardial mass/100 g of body mass, total lipids, cholesterol, triglycerides and phospholipids in blood plasma and the left ventricular myocardium, as well as the plasma free fatty acids, were investigated in 58 male Wistar rats 3,30 and 180 days after operation, in a model of myocardial hypertrophy (MH) induced by experimental coarctation hypertension, after the method of Sclye.An attempt was made to correlate some functional and metabolic indices which characterize the development of this type of MH. On a background of progressively rising BP and parallel increasing R, ECG change were recorded. They were typical of the respective stage of arterial hypertension and MH and expressed mostly in a shifting of the electrical axis of the heart to the left and in essential repolarization disturbances. The most significant changes in the studied lipid fractions were found 30 days after the induction of hypertension. The pathological changes manifested on the 180th day are discussed in relation to age, the stage of hypertension and especially in relation to the developing hypoxic and ischaemic myocardial damage.     

Effects of coronary occlusion on transmural distribution of blood flow in the interventricular septum and left ventricular free wall

Summary Collateral flow to the interventricular septum in the dog was measured after septal artery ligation (N=8) and compared to that in the left ventricular free wall after occlusion of the left anterior descending coronary artery (N=10) in other animals. Flow was quantitated by radiolabelled microsphere injection before, and 90s, 2 h and 4 h after occlusion. Perfusion territory size was measured after colored dye infusion; the septal artery bed occupied 21.74±5.44% of the left ventricle and was significantly smaller than the anterior descending artery zone (40.72±5.44% of the left ventricle and was prior to occlusion was equal in both beds and symmetric across the ventricular wall; endocardial/epicardial and left/right ratios in the anterior descending and septal artery beds were 0.97±0.14 and 1.14±0.17, respectively. 90 s after occlusion, left and right septal and endocardial and epicardial anterior descending flows were significantly (p<0.05) reduced. Right septal flows exceeded left sided flows to produce a transseptal gradient. However, right septal flow was significantly greater than epicardial anterior bed values, and free wall endocardial/epicardial was significantly lower than septal left/right ratios. By 2 h after occlusion, left and right septal flows were no longer significantly different from preocclusion values, whereas anterior descending flows remained significantly below control for the full 4-h period. Thus, significant differences between the two beds exist, with greater acute collateral flows and more rapid correction of flow deficits in the septum than in the free wall.This research was supported by research grants from the American Heart Association. Tennessee Affiliate, from the Veterans Administration, and from the National Heart, Lung and Blood Institute (HL 20597)     

Systemic and regional vascular effects of atrial natriuretic peptide in a rat model of chronic heart failure

Summary To characterize the systemic and regional vascular effects of atrial natriuretic peptide (ANP) in chronic heart failure, central hemodynamics, regional blood flow and plasma ANP levels were determined in a rat model of myocardial infarction and failure and in sham-operated animals. Measurements were made in the conscious state before and after intravenous rANP [99-126] (8 g bolus followed by continuous infusion of 1.0 g/kg/min). With this protocol, ANP significantly decreased cardiac output, right atrial, left ventricular enddiastolic and arterial pressures and there were increases in heart rate, systemic and intestinal vascular resistances in sham animals. Renal blood flow per gram of tissue was unchanged with ANP, but when expressed as a percentage of cardiac output, increased significantly, indicating a preferential renal vasodilatory effect of ANP. In rats with infarction and failure, this dose did not alter cardiac output or arterial pressure, but decreased right atrial and left ventricular blood flow. Although significantly reduced as compared to the control group, renal blood flow was not improved with ANP in the heart failure group. ANP plasma levels of the heart failure group were elevated at baseline (p<0.01), and increased 5–10 times after infusion of rANP. Thus, in rats with chronic heart failure, the renal vascular effects of ANP are blunted, which may, in part, explain the failure of ANP to restore the altered volume homeostasis in heart failure despite elevated ANP plasma levels. However, the effects on venous return were preserved which, in turn, improved cardiac performance via a reduction of preload.Supported by the Deutsche Forschungsgemeinschaft (DFG, Dr 148/3-1)     

Relationship of myocardial morphometry in aortic valve regurgitation to myocardial function and post-operative results

Summary In 24 patients with aortic insufficiency undergoing aortic valve replacement, a clinical and hemodynamic study was performed pre-operatively. Left ventricular biopsies were obtained perioperatively for morphometric study.No significant relations were found when morphometric data were compared to functional class, cardiothoracic radio and ECG findings.The percentage of interstitial fibrosis was not correlated with any of the measured hemodynamic parameters. Myocardial cell diameter was weakly correlated with left ventricular systolic function parameters. A decrease in the percentage of contractile material was strongly correlated with an impaired left ventricular function, assessed pre-operatively. During clinical follow-up, patients were divided into two groups: Group A (17 patients) included patients who were in class I or II of NYHA after surgery. Group B (seven patients) included patients who died or were in functional class III or IV. As compared with Group A, Group B patients had a significantly lower ejection fraction; their myocardial cell diameter was larger and the percentage of myofibrils, and the content of contractile material were significantly lower. This suggests that, in aortic regurgitation left ventricular dysfunction is correlated with contractile material loss and not with interstitial fibrosis, and that morphometric changes are good predictors of follow-up after surgery.     

Three-dimensional analysis of regional mechanical function,blood flow and electrophysiological parameters during early myocardial ischemia in dogs

Summary Ventricular arrhythmias are primarily responsible for sudden cardiac death early after the onset of acute myocardial ischemia. We designed an experimental model to simultaneously characterize regional myocardial function, myocardial blood flow, and electrophysiological parameters, and to determine predisposing factors for the development of early ventricular arrhythmias (EVA).The left circumflex coronary artery was occluded in six anesthetized (n=2 piritramide/N₂O, n=4 chloralose/urethane) mongrel dogs. Systolic wall thickening (% WT) in a control zone and in the central ischemic zone was measured with sonomicrometry and regional myocardial blood flow (RMBF) with colored microspheres. Excitability and relative refractory period at the stimulus electrode and conduction times to all other electrodes were determined with a three-dimensional transmural multi(16)-electrode array using a computer algorithm.In three of six dogs spontaneous EVA occurred 4 to 6 min after coronary occlusion, degenerating to ventricular fibrillation in two of these dogs. The three dogs developing EVA were not distinguished from those not developing EVA, neither by the kind of anesthesia nor by ischemic % WT (–6.6±3.8 [SD] vs –7.8±1.6, ns). Also, dogs with and without EVA did not differ significantly in excitability and relative refractory period. In contrast, dogs with EVA were characterized by a greater mass of severely ischemic myocardium, i.e., exhibiting a RMBF reduction to less than 0.1 ml/(min · g) (18±3 g vs 7±4 g, p<0.05), and by an increase in subendocardial conduction times of greater than 100% above the respective pre-ischemic values (120±18% vs 66±9%, p<0.05). Dogs with and without EVA were not as clearly distinguished by the increases in subepicardial (81±22% vs 46±15%, ns) and transmural (98±31% vs 67±14%, ns) conduction times.The development of EVA is associated with a greater mass of severely ischemic myocardium and a greater increase in subendocardial conduction times.Dedicated to Prof. Dr. Werner Meesmann on the occasion of his 68th birthday     

Alterations in the myocardial capillary vasculature accompany tachycardia-induced cardiomyopathy

Summary Changes in capillary structure and distribution within the left ventricle (LV) occur with pressure and volume overload hypertrophy. These changes may cause an impairment in myocardial blood flow (MBF) and oxygen delivery resulting in myocyte injury and LV dysfunction. However, it is unknown whether changes in the capillary vasculature accompany the development of LV dysfunction in dilated cardiomyopathies. Accordingly, this study examined the relation between LV function, MBF and capillary architecture after the development of dilated cardiomyopathy in pigs produced by chronic supraventricular tachycardia (SVT). LV function was examined by echo-catheterization, and capillary morphometrics were computed using lectin histochemistry in two groups of pigs: sham controls (n=8); and after 3 weeks of pacing-induced SVT (n=8). Chronic SVT resulted in significantly incresed LV end-diastolic dimension and pressure with a 50% reduction in LV fractional shortening compared to CON (p<0.05). Although no significant change in capillary density (2180±164 vs 2402±147/mm², p=0.25) occurred in the SVT group compared to CON, a significant reduction in the volume fraction of capillaries (12.2±0.5 vs 9.9±0.7%, p<0.05) and increased capillary diffusion distance (8.4±0.5 vs 7.5±0.3 m, p<0.05) was observed. Frequency distribution analysis revealed a higher percentage of smaller diameter capillaries with chronic SVT vs CON (p<0.05). Ultrastructural examination revealed an increased capillary-myocyte distance with chronic SVT (0.95±0.08 vs 1.95±0.12 m, p<0.05). These changes were accompanied by ultrastructural evidence of significant subendocardial injury (p<0.05). MBF was measured using microspheres in five additional conscious pigs in each group. MBF was significantly reduced and coronary vascular resistance increased in the SVT group compared to CON (p<0.05). Chronic SVT caused significant remodeling of the capillary vasculature; these changes were associated with reduced MBF, myocyte injury, and LV dysfunction.     

Effect of urapidil on the performance of ischemic myocardium in anesthetized dogs

Summary Urapidil (URA) is used to treat acute hypertension in patients with coronary artery disease, but the effect of URA on the performance of ischemic myocardium has not yet been investigated. The present study was intended to assess the function of ischemic myocardium following URA administration. In eight anesthetized (piritramide) open-chest dogs systolic contraction (dL) and end-diastolic length (edL) of myocardium supplied by the left descending (LAD) and circumflex (LCA) coronary arteries were measured by sonomicrometry simultaneously with aortic pressure (AoP), left ventricular end-diastolic pressure (LVedP), heart rate (HR), stroke volume (SV), and LAD-flow (QLAD). QLAD was reduced by LAD stenosis to about 50% of control, decreasing dLLAD by 55%. Concomitantly, edLLAD increased by about 9% and LVedP by 22%, whereas AoP decreased by 5%. Then, URA was given i.v. (0.25+0.25+0.50+1.0 mg/kg) in 15-min intervals. Following URA, the performance of the non-ischemic area was not systematically affected, but dLLAD increased by about 50%. This could neither be related to the significant reduction in afterload (AoP: –8%), nor to an increase in preload (LVedP and edLLAD did not change significantly), nor to an improved oxygen supply via the LAD (QLAD even decreased), although an increased collateral flow from the LCA could not be excluded. The increase in systolic shortening correlated very closely to a decrease in heart rate (r=–0.92). It is concluded that the improved function of ischemic myocardium following urapidil resulted from a reduced oxygen demand in consequence to the decrease in heart rate.     

The oxygen consumption paradox of “stunned myocardium” in dogs

Summary The contractile state of the heart is a major determinant of myocardial oxygen consumption. Since regional myocardial contractility can be severely impaired following a transient coronary occlusion, post-ischemic myocardium is frequently assumed to consume less oxygen. To test this assumption, regional myocardial function and oxygen consumption were studied in ancsthetized dogs during 2 h of myocardial reperfusion following either a 15-min (Group I) or 4-h (Group II) left anterior descending coronary artery occlusion. Both groups developed similar post-ischemic regional dysfunction characterized by paradoxical motion (negative shortening). Measured as a percent of baseline segment shortening, anterior wall function in Group I (n=8) and Group II (n=5) at 30 min of reperfusion was –33±11% and –34±16% (p=NS) and at 120 min was –23±9% and –40±16% (p=NS). However, the two groups showed a marked difference in regional myocardial oxygen consumption during reperfusion. Despite the abnormal wall motion, regional oxygen consumption in Group I at 30 and 120 min of reperfusion was unchanged from pre-ischemic levels as measured as a percent of bascline: 104±20% (p=NS) and 111±21% (p=NS). In contrast, regional oxygen consumption in Group II was markedly depressed from bascline at 30 and 120 min of reperfusion: 42±7% (p<.01) and 40±8% (p<.01). To determine whether the dissociation between regional myocardial oxygen consumption and function in Group I was related to mitochondrial uncoupling, six additional dogs were studied. Tissue samples were obtained from post-ischemic myocardium after 120 min of reperfusion following a 15-min coronary artery occlusion, and compared to non-ischemic myocardium. There were no differences in the in vitro mitochondrial respiratory rates or oxidative phosphorylation capacity between the post-ischemic and non-ischemic myocardium. Therefore, in the post-ischemic myocardium, significant depressions in regional contractility may not be associated with falls in oxygen consumption. Following a 15-min coronary artery occlusion, the injured myocardium maintains a paradoxically high oxygen consumption with normal mitochondrial function despite decreased contractility and abnormal wall motion.Grant Support: Dr. Dean was a Fellow of the American Heart Association. Dr. Nicklas is supported by the NIH Clinical Investigator Award, HL 011170.     

Open chest and open pericardium affect the distribution of myocardial blood flow in the right ventricle

Summary We have investigated the effects of open chest and open pericardium on the distribution of myocardial blood flow assessed with the radioactive microsphere technique (15 m). Five dogs with intact thorax served as controls (group I) and six dogs were studied after a right-sided thoracotomy and pericardiotomy (group II). Global myocardial blood flow (mean±S.D.) was 0.73±0.17 ml·min^–1·g^–1 in group I and 1.22±0.09 ml·min^–1·g^–1 in group II (p<0.05). Analysis of transmural blood flow distribution revealed that flow was 44% higher in the right and 60% higher in the left ventricular endocardial layers in the open-chest animals, whereas epicardial flow increased by 105% and 90%, respectively. As a result of the preferential blood flow to the epicardial layers of the right ventricle, the endo/epi ratio was reduced from 1.30±0.26 in group I to 0.86±0.11 in the open-chest group (p<0.05). Left ventricular endo/epi ratio was 1.27±0.16 and 1.06±0.11 (n.s.), respectively. External work and diastolic filling pressure of the right ventricle did not differ between the two groups and therefore cannot account for the redistribution of myocardial blood flow. It is concluded that the distribution of myocardial blood flow, particularly in the RV, is severely disturbed by thoracotomy and pericardiotomy. This is an important aspect for the planning and evaluation of studies under open-chest/open-pericardium conditions.Supported by Deutsche Forschungsgemeinschaft grant SFB 320     

Blood flow and blood volume determinations in aorta and in coronary circulation by density dilution

Summary Continuous blood mass-density measurements were performed in anesthetized dogs and injections of 0.7–1.4 ml/kg isotonic saline solution were applied. The resulting density dilution curves were used to compute blood volume, total flow in the aorta and local flow in the coronary circulation. Blood volume calculations were compared with blood volume determined by Evans blue injections and a close agreement was found. Blood flow determined by density dilution was independent from the investigated sites of injection or sampling. We conclude from these results that small volume injections of isotonic saline solution can be used to determine blood volume and flow by density dilution.In addition to these findings, a marked retention of the injected fluid was observed. Possible mechanisms to explain this retention include albumin deposition in the endothelial pores and/or variations of blood viscosity and capillary pressure.     

Effects of dipyridamole on collateral flow and regional myocardial function in conscious dogs with newly developed collaterals

Summary Studies were conducted on six conscious dogs instrumented for measurement of subendocardial segment lengths in the area perfused by the left anterior descending coronary artery (LAD) and left circumflex coronary artery (LCCA), LCCA flow, and left ventricular pressure. Externally inflatable occluders were placed around the proximal LAD and LCCA. Collateral channels sufficient for the resting metabolic demands in the occluded LCCA perfusion territory were induced by repeated, brief LCCA occlusions. Dogs were then subjected to two consecutive brief periods of LAD occlusion. Dipyridamole (0.25 mg/kg) was injected intravenously 3 min prior to the second LAD occlusion. The collateral blood flow from the LCCA to the occluded LAD area was measured as the stepwise decrease in LCCA flow upon release of the LAD occlusion. During LAD occlusion after dipyridamole treatment collateral blood flow velocity decreased to 3.8±1.1 cm/s (±standard error) compared with a value of 4.9±0.9 cm/s measured during LAD occlusion without dipyridamole treatment. Percentage systolic segment shortening in the collateral dependent zone significantly deteriorated from 14.3±5.2 to 9.7±5.0% (p<0.05). Electrocardiograms taken simultaneously from endocardial ultrasonic transducers in the ischemic segment revealed significant increases in ST-segment level from 4.2±0.6 to 5.4±0.6 mV. These findings indicate that dipyridamolc adverscly affects the extent of myocardial ischemia in the collateral-dependent zone.Supported by grant HL 32800 from the NHLBI     

Left ventricular wall stress distribution in chronic pressure and volume overload: effect of normal and depressed contractility on regional stress-velocity relations

Summary Regional stress-velocity relations were determined in a first group of patients (n=15) with normal (five controls, five patients with aortic stenosis, and five patients with aortic insufficiency) and a second group of patients (n=10) with depressed contractility (five patients with aortic stenosis and five with aortic insufficiency). LV circumferential wall stress was calculated from high-fidelity pressure and frame-by-frame angiocardiographic data using the Wong thick-wall model. Regional wall stress and shortening velocity were calculated from the endo-to the epicardium, and from the equator to the apex at 35 points.Regional LV wall stress was in all patients lower at the epi- than the endocardium, and lower at the apex than the equator. Regional stress-velocity relations were downward shifted from the endo- to the epicardium and from the equator to the apex (family of curves) in both groups. At corresponding LV regions stress-velocity relations showed significantly smaller slopes and intercepts (downward depression) in group 2 than in group 1.Thus, wall stress distribution is inhomogeneous in the normal, as well as in the pressure and volume overloaded left ventricle. Regional differences in stress-velocity relations within groups (family of curves) are probably related to changes in preload rather than to changes in regional contractility. Downward depression of the regional stress-velocity relations in group 2 is caused by depressed myocardial contractility.Supported by the Swiss National Science Foundation     

The relationship between regional blood flow and contractile function in normal,ischemic, and reperfused myocardium

Summary The prevailing paradigm of coronary physiology and pathophysiology is that a balance between blood flow (i.e., supply) and function (i.e., demand) exists under normal conditions and that an imbalance between supply and demand occurs during ischemia. However, this paradigm is derived largely from studies relating changes in total coronary inflow to global ventricular function. The present article examines the relationship between myocardial blood flow and function on a regional level and proposes that a change may be needed in the current paradigm of coronary pathophysiology. In normal myocardium, considerable heterogeneity of regional blood flow exists, indicating either similar heterogeneity of metabolic demand and function or questioning the precision of metabolic coupling between flow and function. After the onset of ischemia, a transient imbalance between the reduced blood flow and function may exist. However, myocardial function rapidly declines and during early steady-state ischemia regional myocardial blood flow and function are once again evenly matched. Such supply-demand balance may persist over prolonged periods of ischemia enabling the myocardium to remain viable through reduction of energy expenditure for contractile function, i.e., to hibernate. Whereas in hibernating ischemic myocardium, regional myocardial blood flow and function are both reduced but appropriately matched to one another, flow and function appear to be largely uncoupled in reperfused stunned myocardium. The clinical identification of viable but ischemic (hibernating) and postischemic (stunned) myocardium is of utmost importance in patients undergoing reperfusion procedures. A new paradigm of coronary and myocardial pathophysiology, encompassing a regional as well as a global view of perfusion and function, will have to include explanations for phenomena such as myocardial hibernation and myocardial stunning.     

High-energy phosphates,myocardial contractile function and material properties after short periods of oxygen deficiency

Summary To investigate myocardial performance and diastolic properties after repeated periods of oxygen deficiency auxotonic and isovolumic measurements were performed after three periods (4 min) of asphyxia in Wistar rats (n=19). Additionally, the response of the peak isovolumic left ventricular pressure to postextrasystolic potentiation was measured. The hemodynamic results were compared to the levels of high-energy phosphates.Already after 15 min of recovery from asphyxia auxotonic measures of systolic function were completely normal compared to the control group (n=19). Isovolumic measurements after 20 min of postasphyctic recovery, however, demonstrated a considerable reduction of the peak left ventricular pressure (226.5±7.5 mm Hg vs. 262.6±3.4 mm Hg in controls, mean±SEM (p<0.01)) indicating persistence of decreased postischemic contractile performance. The relative effect of postextrasystolic potentiation was similar in both groups, but could not compensate for the reduced performance of the postasphyctic hearts: the absolute postextrasystolic peak isovolumic pressure of the postasphyctic hearts was lower than the value of the regular isovolumic peak pressure in the controls. Diastolic properties (pressure/volume and stress/strain relationships) of the postasphyctic myocardium remained unchanged. The total sum of the adenine-nucleotides decreased from 7.2±0.2 to 5.6±0.3 mol/gww (p<0.01). ATP was reduced from 4.8±0.2 to 3.9±0.3 mol/gww (p<0.01). Phosphocreatine was elevated to 7.0±0.6 mol/gww, x±SEM (p<0.01).Our results demonstrated normal postasphyctic basal hemodynamics and material properties. Thus, the energy supply was sufficient to maintain steady state conditions — in spite of decreased overall adenine-nucleotide levels. Isovolumic measurements and postextrasystolic potentation tests, however, indicated that the contractile performance of the postischemic myocardium was still reduced. This functional limitation cannot be explained by altered material properties and is probably not causally related to the decreased overall ATP content.Parts of the results were presented at the 10th World Congress of Cardiology, Washington D.C., USA, 1986Supported by the Deutsche Forschungsgemeinschaft (DFG), Bonn (Ho 1003/1-1)     

Superoxide dismutase and catalase do not improve recovery of regional myocardial contractile function when given at the time of reperfusion after reversible regional ischemia in anesthetized dogs

Summary Earlier studies have demonstrated an improvement in the recovery of the regional myocardial function after reversible myocardial ischemia when dogs were treated with superoxide dismutase (SOD) + catalase (CAT). In all these studies, drug administration was started prior to the ischemic period. The aim of this study was to investigate the effects of SOD and CAT on the recovery of the regional contractile function in anesthetized beagle dogs when the drugs were administered at the time of reperfusion. The animals were subjected to 20 min of left coronary artery occlusion followed by 3 h reperfusion. The regional myocardial contractile function, measured as subendocardial segment shortening (SS, sonomicrometry) decreased to below zero and the regional blood flow in the ischemic subendocardium was reduced to about 5 % of pre-ischemic values during the coronary artery occlusion period. The size of the occluded bed was similar in the two groups. Saline (n = 8) or SOD (10 mg/kg) + CAT (3.4 mg/kg) (n = 8) were infused into the left atrium from 2.5 min prior to until 20 min after the start of reperfusion. The peak plasma level of SOD was 102 ± 15 mg/1 at 20 min reperfusion. There were no significant differences in the arterial blood pressure, cardiac contractile function and regional blood flow between the two groups at any time during the experiment. During reperfusion in the dogs given vehicle, SS recovered to 48 ± 7 % (mean ± SEM) after the first hour of reperfusion, and to 51 ± 6 % of pre-ischemic values after 3 h of reperfusion. The corresponding values in SOD + CAT treated dogs were 50 ± 5 % (1 h) and 53 ± 8 % (3 h), respectively. It is concluded that SOD + CAT, when given at the time of reperfusion, did not improve the regional contractile function after reversible ischemia in the anesthetized beagle dog.     

Diameters and segment relations during the cardiac cycle in the canine left ventricle

Summary The relations between left ventricular antero-posterior, septum-free wall diameters and an anterior subendocardial segment were studied by sonomicrometry in seven open-chest anesthetized dogs, during the control state and during left ventricular and right ventricular pressure overload for low and high left ventricular filling pressures. A linear relationship between antero-posterior and septal-free wall shortening was observed during control and during left ventricular pressure overload when left ventricular filling pressure was high. For low end-diastolic ventricular pressure, there was the same relationship during ejection with an isovolumic lengthening of the septal-free wall diameter. This relationship was shifted downwards during pulmonary artery stenosis for both high and low left ventricular filling pressure, which produced a significant decrease in end-diastolic septum-free wall diameter without significant modifications of end-diastolic antero-posterior diameter. The anterior segment exhibited behavior similar to that of the calculated left ventricular circumference. Subendocardial anterior segment measurements in the open-chest dog model can be used as indices of left ventricular circumference.