Left Ventricular Function Curves Research Articles

Haemodynamic and electrophysiological acute toxic effects of mercury in anaesthetized rats and in langendorff perfused rat hearts

The acute toxic effects of HgCl2 on the cardiovascular system were studied in Langendorff-perfused rat hearts and in anaesthetized rats. Isovolumic systolic pressure (ISP), atrial and ventricular rates, and atrioventricular conduction (PR-interval) were studied in the hearts perfused with bicarbonate buffer Krebs solution, at 31 degrees C, under a constant pressure of 75 mmHg. Eight hearts were studied at a fixed rate (200 bpm) under control conditions and at different HgCl2 concentrations (0.1, 1 and 10 microM). In these preparations the left ventricular function curves showed that Hg2+ reduces ISP development in a concentration-dependent manner whilst the myocardial response to increasing diastolic pressure is preserved. Ten additional spontaneously beating hearts were studied also under control conditions and at several HgCl2 concentrations (0.5, 1, 2 and 10 microM). ISP and ECG were recorded. Again, ISP decreased after Hg2+ treatment, but all HgCl2 concentrations produced effects of the same magnitude. The reduction of heart rate that also occurs during Hg2+ treatment is the possible explanation for the different effects of Hg2+ on the ISP obtained from the driven and spontaneously beating preparations. Hg2+ also decreased the atrial and ventricular rate driven by atria and increased the PR-interval. Several arrhythmias were induced, such as extrasystoles, A-V blocks, brady- and tachyarrhythmias and ventricular fibrillation without a clear relationship with Hg2+ concentrations. The possibility of an increased activity of autonomic neurotransmitters was also investigated. Cholinergic activity was evaluated in 14 preparations and adrenergic activity in eight by blocking their effects with atropine (0.2 micrograms ml-1) and propranolol (0.1 microgram ml-1), respectively. Atropine reduced Hg2+ effects on ISP, heart rate and PR-interval while propranolol enhanced the cholinergic effects. In the anaesthetized rats the changes in mean arterial blood pressure (MBP), heart rate (HR), and atrioventricular conduction (PR-interval) were recorded and followed for 120 min. In five rats acute poisoning was achieved using a high dose of HgCl2 (50 mg kg-1). MBP and HR decreased and PR-interval increased. Arrhythmias developed followed by ventricular fibrillation and all the animals died after 1 min. In nine other rats a lower dosage (5 mg kg-1) was used. MBP and HR decreased progressively and the PR-interval increased after 40 min. Using the same protocol, six other rats were pretreated with propranolol (2 mg kg-1), and seven with atropine (1 mg kg-1). Propranolol delayed the reduction in MBP caused by HgCl2. HR decreased after propranolol injection but did not change thereafter. The PR-interval, however, increased significantly within the first minute after HgCl2 injection. Atropine blocked the changes in MBP, HR and PR interval produced by HgCl2 during 120 min of observation. Another group treated with 0.5 mg kg-1 was also studied but no changes of the parameters analysed were observed. The results suggest that, in addition to the reduction of mechanical activity, Hg2+ affects heart rate and atrioventricular conduction, has arrhythmogenic effects, decreases arterial blood pressure and increases autonomic neurotransmitter activity.

Cardiovascular actions of atrial natriuretic factor in sheep with cardiac failure.

The present study examines in detail the short-term cardiovascular actions of atrial natriuretic factor (ANF) in sheep with experimental low-output cardiac failure. Five conscious sheep, surgically implanted with a ventricular pacing wire, were paced at 220 beats/min for 14 days. Most clinical symptoms of congestive heart failure (CHF) were apparent after the 14 days, characterized by low cardiac output, high venous pressure, increased total peripheral resistance, increased plasma levels of ANF, noradrenaline, arginine vasopressin and renin, and marked fluid retention. On day 14 of pacing, intravenous infusion of ANF at 100 micrograms/h for 60 min restored cardiac output to prepacing values and reduced both total peripheral resistance and right atrial pressure. These effects were sustained throughout the infusion period. No change was seen in blood pressure, plasma renin, or noradrenaline levels. These hemodynamic changes, produced by short-term infusion of ANF, contrasted with those seen in normal sheep, where there was a fall in cardiac output with increased total peripheral resistance. These changes reflect a return toward normal of the left ventricular function curve. This is the first study to report that ANF improves cardiac function in conscious sheep with CHF, primarily by a vasodilator action to reduce cardiac preload, and suggests that ANF may be useful in treating the hemodynamic effects associated with cardiac failure.

Cardiovascular Actions of Atrial Natriuretic Factor in Sheep With Cardiac Failure

The present study examines in detail the shortterm cardiovascular actions of atrial natriuretic factor (ANF) in sheep with experimental low-output cardiac failure. Five conscious sheep, surgically implanted with a ventricular pacing wire, were paced at 220 beats/min for 14 days. Most clinical symptoms of congestive heart failure (CHF) were apparent after the 14 days, characterized by low cardiac output, high venous pressure, increased total peripheral resistance, increased plasma levels of ANF, noradrenaline, arginine vasopressin and renin, and marked fluid retention. On day 14 of pacing, intravenous infusion of ANF at 100 μg/h for 60 min restored cardiac output to prepacing val ues and reduced both total peripheral resistance and right atrial pressure. These effects were sustained throughout the infusion period. No change was seen in blood pressure, plasma renin, or noradrenaline levels. These hemodynamic changes, produced by short-term infusion of ANF, contrasted with those seen in normal sheep, where there was a fall in cardiac output with increased total peripheral resistance. These changes reflect a return toward normal of the left ventricular function curve. This is the first study to report that ANF improves cardiac function in conscious sheep with CHF, primarily by a vasodilator action to reduce cardiac preload, and suggests that ANF may be useful in treating the hemodynamic effects associated with cardiac failure. Am J Hypertens 1994; 7:905–912

Left ventricular preload reserve in preterm infants with patent ductus arteriosus.

The left ventricular Frank-Starling response was studied in 15 preterm infants, less than 1500 g birth weight, and in 16 fullterm infants with patent ductus arteriosus. Left ventricular end diastolic volume (LVEDV), stroke volume, and cardiac output were calculated from biplane echocardiographic images with a modified Simpson's rule, and the left ventricular function curve was obtained by standardising with birth weight and body length. In the relationship between LVEDV and stroke volume, the slope of the regression line was significantly milder in preterm than in fullterm infants; however, there was no significant difference in the relationship between LVEDV and cardiac output. The heart rate was significantly higher in preterm than in fullterm infants. Our data indicated that the premature infants had less left ventricular reserve capacity to respond to the increased preload through the left-to-right ductal shunting than the mature ones, and that the high pulse rate made it possible to generate adequate cardiac output in premature infants.

The Effect of Peep-ventilation on Cardiac Function in Closed Chest Pigs

Does ventilation with positive end-expiratory pressure (PEEP) depress myocardial contractility? Ten piglets were anaesthetized and prepared for the measurement of cardiac output (SV) and right (MRAPtm) and left (MLAPtm) mean transmural atrial pressure, the latter serving as indices of preload. 500 ml of autologous blood was re-transfused during intermittent positive pressure ventilation without PEEP (IPPV) and continuous positive pressure ventilation with 15 cm H2O PEEP (CPPV). Right and left ventricular function curves were drawn by plotting MRAPtm and MLAPtm respectively versus the corresponding strokevolumes before and after re-transfusion. Similar inclinations were obtained during IPPV and CPPV on either side of the heart. Although the ventricular function curves during IPPV and CPPV covered partially different preload levels, the results suggest that CPPV i.e. PEEP does not affect myocardial contractility.

Free Radical Scavengers Prevent Intestinal Ischemia-Reperfusion-Mediated Cardiac Dysfunction

Our previous studies show that intestinal ischemia impairs cardiac function. This present study examined the contribution of oxygen-derived free radicals to cardiac dysfunction after intestinal ischemia-reperfusion in a rat model of superior mesenteric artery (SMA) occlusion (atraumatic clip for 20 min) and ligation of collateral arcades from the right colic and jejunal arteries. Controls were sham operated (Group 1, n = 10); in Group 2, 20 rats with SMA occlusion were sacrificed 2-5 hr after reperfusion without treatment. Superoxide dismutase (SOD) and catalase, scavengers of oxygen-derived free radicals which have been shown to effectively reduce ischemic injury in several models of traumatic injury, were given as 6000 units/350 g body wt either 1 min after SMA occlusion (Group 3, n = 11) or 2 min after reperfusion (Group 4, n = 10). To examine the contribution of neutrophils as a source of free radicals, additional groups of animals were treated with pentoxifylline (PTX, a methylxanthine derivative which has been shown to decrease neutrophil adherence and aggregation as well as to decrease superoxide production) either 1 min after SMA occlusion (Group 5, n = 10) or 2 min after reperfusion (Group 6, n = 10). Cardiac contractile depression occurred in the untreated ischemic group as indicated by a fall in left ventricular pressure (from 77 ± 3 to 63 ± 4 mm Hg, P < 0.01) and + dP/dt max (from 1827 ± 60 to 1558 ± 98 mm Hg/sec, P < 0.03) and - dP/dt max (from 1267 ± 57 to 953 ± 68 mm Hg/sec, P < 0.02). Contractile depression after untreated ischemia-reperfusion was confirmed by a rightward shift in left ventricular function curves and decreased responsiveness to perfusate calcium. Both free radical scavengers (SOD and catalase) and neutrophil stabilization (PTX) prevented ischemia-reperfusion-mediated cardiac dysfunction, and left ventricular function curves for these treated groups were identical to those generated by control hearts. We conclude that oxygen-derived free radicals from activated neutrophils contribute, in part, to intestinal ischemia-reperfusion-mediated cardiac dysfunction.

Cardiac Contractile and Calcium Transport Function after Burn Injury in Adult and Aged Guinea Pigs

Cardiac dysfunction occurs after a major burn injury regardless of age; whether burn trauma causes greater myocardial contractile depression in the older subject due to reduced cardiac reserves that normally occur with adult aging is not known. The cellular basis for burn-induced cardiac dysfunction is not known, but several studies have suggested that alterations occur in the rate of Ca2+ delivery to the contractile proteins as well as in the rate of Ca2+ removal from the sarcoplasm by the sarcoplasmic reticulum (SR). To determine if agerelated differences in the cardiac contractile response to burn injury are associated with differences in SR Ca2+ transport, an isolated heart preparation was used to examine mechanical function, and myocardial homogenate preparations were used to assess SR Ca2+ transport. Guinea pigs from both age groups (adult, 6-8 months, and senescent, 34-36 months of age) were divided into two subgroups—control and 45% cutaneous scald burn. Cardiac dysfunction associated with adult aging alone was indicated by lower systolic pressure and lower rates of left ventricular (LV) pressure rise and fall, as well as decreased responses to isoproterenol, exogenous Ca2+, increased coronary flow rate, and electrical pacing. Myocardial depression in senescent control hearts was accompanied by a decreased maximal Ca2+ uptake in myocardial homogenates, suggesting that altered SR calcium transport may contribute to the diminished contractile function associated with aging. Burn injury impaired cardiac function in all animals regardless of age as evidenced by a leftward shift of LV function curves and altered responses to receptor- and nonreceptor-mediated inotropic interventions. However, the percentage change in cardiac function after burn injury was similar in both age groups compared to those of their respective controls. Significant alterations in SR Ca2+ transport were observed in myocardial homogenates isolated from both adult and senescent hearts after burn injury. Our data confirm that burn injury induced cardiac contractile dysfunction as well as alterations in SR Ca2+ transport function regardless of age, and we conclude that altered SR Ca2+ transport function contributes, in part, to the diminished cardiac function after burn injury.

Diminished cardiac contractile response to burn injury in aged guinea pigs.

Previous studies have shown that regulation of the cardiovascular system progressively deteriorates with adult aging, limiting cardiovascular adaptive mechanisms to stress such as aerobic exercise or trauma. This present study examined cardiac contractile performance as a function of adult aging in a guinea pig model and secondarily examined the effects of adult aging on cardiac contractile responses to burn injury. In a total of 39 adult and 49 senescent animals, a cutaneous full-thickness burn comprising 45% of the total body surface area was obtained using a template device (Walker model); a sham burn was produced in 38 adult and 35 senescent animals by immersion in room temperature water. Adult aging altered cardiac contraction and relaxation as indicated by significantly lower left ventricular pressure and +/- dP/dt max, as well as diminished left ventricular responsiveness to increases in preload, perfusate calcium, isoproterenol, and calcium channel blockade. Burn injury caused significant hypotension, hypothermia, and a rise in hematocrit regardless of age. Cardiac contractile dysfunction occurred in all hearts after burn injury regardless of age, as indicated by a rightward and downward shift of left ventricular function curves for both burn groups compared with their respective controls. The failure of increasing perfusate calcium to overcome burn-mediated contractile deficits in both age groups suggested that burn injury disrupts sarcolemma-bound calcium. The burn-induced decrease in negative inotropic potency of a calcium channel blocker suggests that burn injury specifically targets the calcium slow channel of the sarcolemma.(ABSTRACT TRUNCATED AT 250 WORDS)

Full-thickness dynamic cardiomyoplasty of the left ventricle with free revascularized latissimus dorsi myografts

Dynamic cardiomyoplasty, with use of a free latissimus dorsi myograft revascularized by the internal thoracic artery and vein, was performed in eight dogs subjected to electrical preconditioning for 8 to 12 weeks (group I) and in six unconditioned dogs (group II). The procedure was performed after the resection of the anterior wall of the left ventricle. Cardiac output and left ventricular stroke work were augmented by 23.7% +/- 9.4% and 44.1% +/- 15.9% after graft pacing with 50 Hz burst stimulation at a 1:1 synchronization ratio, while left atrial pressure ranged from 8 to 12 mm Hg. Analysis of the left ventricular function curve showed that graft pacing at rates of 1:1, 2:1, and 3:1 augmented global left ventricular function. Hemodynamic benefit by continuous pacing at a 3:1 ratio was seen for 1.97 +/- 1.90 hours (0.5 to 6.1 hours) in group I until complications unrelated to the graft terminated the study, while it lasted for only 0.19 +/- 0.09 hour in group II. During the stimulation, the ratio of the lactate output to the oxygen consumption of the graft in group I, a possible indicator of metabolic shift, was significantly less than in group II, (0.46 +/- 0.58 and 6.34 +/- 1.73; p < 0.01). We conclude that free grafts of transformed latissimus dorsi muscle can augment global left ventricular performance, with a physiologic preload by oxidative metabolism, and provide a viable option in full-thickness dynamic cardiomyoplasty.

Cardiac factors in orthostatic hypotension

Cardiac function is determined by preload, afterload, heart rate and contractility. During orthostatic stress, the footward blood shift is compensated for by an increase of afterload. LBNP is widely used to analyze effects of volume displacement during orthostatic stress. Comparisons of invasive ( right heart catheterization) and non-invasive approach (echocardiography) yielded similar changes. Preload and afterload change with graded LBNP, heart rate increases, and stroke volume and cardiac output decrease. Thus, the working point on the left ventricular function curve is shifted to the left and downward, similar to hypovolemia. However, position on the Frank-Starling curve, the unchanged ejection fraction, and the constant Vcf indicate a normal contractile state during LBNP. A decrease of arterial oxygen partial pressure during LBNP shwos impaired ventilation/perfusion ratio. Finally, LBNP induced cardiac and hemodynamic changes can be effectively countermeasured by dihydroergotamine, a potent venoconstrictor. Comparison of floating catheter data with that of echocardiography resulted in close correlation for cardiac output and stroke volume. In addition, cardiac dimensions changed in a similar way during LBNP. From our findings, echocardiography as a non-invasive procedure can reliably used in LBNP and orthostatic stress tests. Some informations can be obtained on borderline values indicating collaps or orthostatic syncope. Early fainters can be differentiated from late fainters by stroke volume changes.

U-74, 500A inhibition of burn-induced cardiac dysfunction

Our previous studies suggest that oxygen-derived free radicals, particularly the hydroxyl radical, play a major role in cardiac dysfunction which is characteristic of burn injury. In this present study, we examined the effects of U-74,500A (U7), a 21-aminosteroid, nonglucocorticoid on ventricular contraction and relaxation recovery from burn injury. Parameters measured included left ventricular pressure (LVP) and the maximal rate of LVP rise (+dP/dt max) and fall (−dP/dt max). Full-thickness burns comprising 45% of the total body surface area (burn groups, N = 69) or 0% for controls (Group 1, N = 8) were produced in guinea pigs. In Group 2, 20 burned guinea pigs were not fluid resuscitated (vehicle only) and served as untreated burns; in Group 3, 11 burned guinea pigs received U7 alone (2.5 mg/kg in 0.01 N HCl iv). Eleven burned guinea pigs were resuscitated with vehicle plus 4 ml lactated Ringer's (LR)/kg/% burn for 24 hr (Group 4); in Group 5, 14 guinea pigs were treated with U7 as described for Group 3 followed immediately by LR for 24 hr as described for Group 4. In Group 6, U7 was administered immediately postburn as described for Group 3; and LR resuscitation, begun 1 hr postburn, was continued for 24 hr ( N = 14). Compared to controls, untreated burn injury significantly impaired cardiac function as indicated by a fall in LVP (74 ± 3 vs 60 ± 4 mm Hg, P < 0.05) and ± dP/dt max (1126 ± 51 vs 1011 ± 39 and 1159 ± 53 vs 993 ± 59 mm Hg/sec, P < 0.05, respectively). Neither fluid resuscitation with LR alone or U7 alone improved burn-induced cardiac dysfunction. In contrast, U7 given postburn and followed with either immediate or delayed fluid resuscitation significantly improved cardiac contractile function. Hearts treated with U7 and fluid resuscitation delayed for 1 hr postburn generated left ventricular function curves (LVP and + dP/dt max plotted vs LV end-diastolic volume) comparable to those calculated for control hearts. These data suggest that antagonizing free radical mediated, iron catalyzed lipid peroxidation improves cardiac function after burn injury, indicating a therapeutic role for the 21-aminosteroids in burn shock.

Hemodynamic basis for cocaine-induced pulmonary edema in dogs

We tested the hypothesis that cocaine-induced impairment of left ventricular function results in cardiogenic pulmonary edema. Mongrel dogs, anesthetized with alpha-chloralose, were injected with two doses of cocaine (5 mg/kg iv) 27 min apart. Cocaine produced transient decreases in aortic and left ventricular systolic pressures that were followed by increases exceeding control. As aortic pressure recovered, left ventricular end-diastolic, left atrial (Pla), pulmonary arterial (Ppa), and central venous pressures rose. Cardiac output and stroke volume were reduced when measured 4-5 min after cocaine administration. Peak Ppa and Pla were 31 +/- 5 (SE) mmHg (range 17-51 mmHg) and 26 +/- 5 mmHg (range 12-47 mmHg), respectively. Increases in extravascular lung water content (4.10 to 6.24 g H2O/g dry lung wt) developed in four animals in which Pla exceeded 30 mmHg. Analysis of left ventricular function curves revealed that cocaine depressed the inotropic state of the left ventricle. Cocaine-induced changes in hemodynamics spontaneously recovered and could be elicited again by the second dose of the drug. Our results show that cocaine-induced pulmonary hypertension, associated with decreased left ventricular function, produces pulmonary edema if pulmonary vascular pressures rise sufficiently.

Left ventricular dynamics and plasma catecholamines during isometric exercise in patients following cardiac transplantation

Haemodynamics and plasma catecholamine responses to isometric exercise were evaluated invasively in 11 orthotopic heart transplant recipients and seven control subjects. Differences in haemodynamic responses between the two groups were already apparent after one min of handgrip at 30% of maximal voluntary contraction, and very pronounced at the end of the fourth minute. At this point transplanted patients showed smaller increments in heart rate (4.8 +/- 3.2 vs 20.4 +/- 14.1 beats.min-1, P less than 0.001), mean arterial pressure (13.7 +/- 7.2 vs 31.5 +/- 12.2 mmHg, P less than 0.001) and cardiac index (0.51 +/- 0.22 vs 1.02 +/- 0.53 L.min-1.m-2, P less than 0.01), whereas left ventricular end-diastolic pressure increased to a greater extent (8.8 +/- 4.9 vs 2.2 +/- 1.8 mmHg, P less than 0.01). Stroke volume index increased similarly (3.8 +/- 1.8 vs 2.0 +/- 3.5 ml beat-1.m-2, NS) and systemic vascular resistance remained unchanged in both groups. The slopes of the left ventricular function curves (ratio of change in left ventricular work to change in left ventricular end-diastolic pressure) indicated depressed left ventricular function in the transplanted patients. The two groups showed similar increments in mixed venous plasma norepinephrine and epinephrine indicating normal sympathoadrenal activation in the transplanted patients. In conclusion, transplanted hearts respond to handgrip with attenuated increases in heart rate, cardiac output and arterial pressure and by increasing left ventricular filling pressure, suggesting a poor contractile reserve probably due to denervation. Circulating catecholamines, especially epinephrine, probably contribute to the cardiac responses to isometric exercise.

Systolic and diastolic dysfunction of the left ventricle induced by dietary taurine deficiency in cats

Isovolumic left ventricular (LV) preparations were used to assess myocardial failure associated with dietary taurine deficiency in cats. Adult female cats (n = 12) were fed a purified diet devoid of taurine for 6-8 mo. Six of the cats received 1,000 mg of crystalline taurine orally once daily. The remaining six cats were not provided taurine replacement. Compared with control preparations, hearts isolated from taurine-deficient cats generated significantly lower values for developed LV systolic pressure (107 +/- 6 vs. 66 +/- 15 mmHg; P less than 0.05), maximal rate of LV pressure rise (+dP/dtmax; 1,103 +/- 38 vs. 718 +/- 172 mmHg/s; P less than 0.05), and fall (-dP/dtmax; 930 +/- 46 vs. 587 +/- 129 mmHg/s; P less than 0.05). LV function curves generated by hearts from taurine-deficient cats were shifted downward and to the right of control curves, demonstrating inotropic depression. In addition, end-diastolic pressure-volume (compliance) relationships in hearts from taurine-deficient cats were shifted downward and to the right of controls in the direction of increased chamber compliance or distensibility. Ten millimolar taurine significantly improved inotropic indexes only in hearts from taurine-deficient cats but failed to affect diastolic compliance. Myocardial contractile dysfunction and LV chamber dilatation in hearts from taurine-deficient cats verify a causal association between dietary deficiency of this amino acid and dilated cardiomyopathy in this species.

Changes in performance of the surviving myocardium after left ventricular infarction in rats

The aim was to investigate left ventricular performance of infarcted hearts during scar formation and development of hypertrophy in the surviving myocardium. Hearts were perfused according to the Langendorff technique and left ventricular function curves were obtained by inserting a distensible balloon into the ventricular cavity. The isovolumetric systolic pressure was measured as diastolic pressure was changed from 0 to 25 mm Hg and during inotropic interventions produced by Ca and isoprenaline. Hearts were obtained from albino rats of either sex, 180-250 g, killed 1, 3, 7 or 14 d after left coronary artery ligation (n = 24) or sham operation (n = 26). Normal rats (n = 6) were used as additional controls. After infarction, there was a progressive and almost parallel displacement of the ventricular function curves toward higher diastolic pressures. The positive chronotropic response to isoprenaline was similar in infarcted and non-infarcted hearts. The inotropic response to Ca and isoprenaline, however, was significantly depressed in the infarcted hearts throughout the observation period. Hypertrophy in the surviving myocardium did not result in improvement of the left ventricular systolic function assessed under in vitro conditions during the first two weeks after infarction. The decreased inotropic response of the infarcted left ventricle to isoprenaline is likely to be dependent on the reduced Ca sensitivity of the surviving myocardium.

Effect of preload change on resting and exercise cardiac performance in hypertrophic cardiomyopathy

The purpose of this study was to investigate the hemodynamic responses, at rest and on exercise, of patients with hypertrophic cardiomyopathy to changes in circulating volume. After Swan-Ganz and radial arterial cannulation, 13 patients with hypertrophic cardiomyopathy performed maximal exercise tests after diuretic (frusemide 20 mg intravenously) and after fluid loading (0.9% saline at 10 ml/kg body weight intravenously) on different days. At rest, right atrial and pulmonary capillary wedge pressures increased with volume loading and decreased with a diuretic. There were no significant changes in the resting, supine cardiac or stroke indexes but in the upright position, the cardiac index and stroke index were higher after volume loading (2.5 ± 0.7 vs 2.2 ± 0.5 liters/min/m 2, p < 0.05; 33 ± 11 vs 27 ± 9 ml/m 2, p < 0.005, respectively). Although the right atrial, pulmonary arterial and pulmonary capillary wedge pressures were higher during exercise after volume loading, there were no significant differences in exercise heart rate, systemic blood pressure, cardiac index, stroke index, systemic vascular resistance index or overall exercise capacity compared to exercise after diuresis. The data show that the cardiac index and stroke index, at supine rest and during upright exercise, were not influenced by the preload changes induced in these patients with hypertrophic cardiomyopathy. The results suggest that these patients are operating on the plateau of left ventricular Frank-Starling function (filling pressure/output) curve.

Effects of nifedipine on left venticular diastolic dysfunction after myocardial infarction

In order to assess the effects of nifedipine on left ventricular diastolic abnormalities, 26 patients (mean age 52 year, range 42-66) were studied 10 days after a first myocardial infarction, at rest and during handgrip by Doppler examination. The time-velocity integral for the rapid (E) and atrial (A) filling phases and the E/A ration were used; stroke volume was calculated as the aortic time-velocity integral times the cross-sectional valvular area. Twenty age-matched normal subjects constituted the controls. Twenty-one patients had a reversal of the early to late diastolic filling pattern; five patients had a restrictive pattern. Nifedipine normalized left ventricular filling in patients with a reverse pattern, both at rest and during handgrip. Moreover, these patients showed a descending left ventricular function curve by relating at rest and handgrip values of cardiac index and the E/A ratio. After nifedipine, these study patients showed an ascending left ventricular curve, similar to that of normal subjects, with an increase in cardiac index and a slight decrease in the E/R ratio. No beneficial effects were detectable in patients with a restrictive pattern of left ventricular filling.

Excessive Sympathetic Nervous System Activity Decreases Myocardial Contractility

The objective of this study was to determine whether myocardial contractility is depressed by intense activation of the sympathetic nervous system. A massive sympathetic discharge was produced by injecting veratrine or sodium citrate into the cisterna magna of anesthetized rabbits (n = 10). Two and one-half hr later, the hearts were isolated and their left ventricular (LV) performance evaluated and compared with the LV performance of hearts isolated from control animals (n = 10). LV performance was evaluated from steady-state peak isovolumic systolic and end-diastolic pressures that were generated at various end-diastolic volumes (LV function curves). The relationship between peak LV systolic pressure (or the average peak developed LV wall stress) and LV end-diastolic volume was rotated downward (P less than 0.01) in the hearts removed from rabbits treated with veratrine or citrate. The LV end-diastolic pressure or LV end-diastolic wall stress of these hearts was not different from control at any end-diastolic volume. The diminished ability of the experimental hearts to develop systolic pressure or wall stress suggests that intense sympathetic activation depressed contractility. Severely damaged myofibers, located largely in the subendocardium, were found in these hearts. Furthermore, the depressed contractility was not related to pulmonary edema since only 2 of 10 rabbits developed edema.

Hypertonic Saline Solution-Hetastarch for Fluid Resuscitation in Experimental Septic Shock

Hypertonic colloid solutions have been found efficacious in the resuscitation from hemorrhagic/traumatic shock. The present study investigated the hemodynamic, gasometric, and metabolic effects of hypertonic colloids in endotoxic shock in the dog. Thirty minutes after administration of 3 mg/kg normal body weight of Escherichia coli endotoxin, dogs were randomly assigned to receive 10 mL/kg hydroxyethylstarch (HES) either in 0.9% NaCl (HES, 10 dogs) or in 7.5% NaCl (HT-HES, 10 dogs) in 30 min. Thereafter, 0.9% NaCl solution was administered in volumes adequate to maintain pulmonary artery balloon-occluded pressure at baseline levels. Total fluid administered averaged 64 +/- 30 mL/kg (mean +/- SD) in the HES group and 73 +/- 34 mL/kg in the HT-HES group. As these differences were not statistically significant, total sodium load was higher in the HT-HES group. The persistent volume effect was associated with persistently lower hematocrit and protein levels in the HT-HES group. Initial fluid resuscitation with HT-HES resulted in arterial pressure, cardiac filling pressures, cardiac output, stroke volume, and rates of oxygen delivery and oxygen consumption that were greater than those with HES. Vascular resistances were similar. Analysis of left ventricular function curves also indicated an improvement in cardiac performance. However, these effects almost completely vanished during the remainder of the study. In the HT-HES group, serum sodium and osmolality levels increased to 167 +/- 4 mEq/L and 344 +/- 4 mOsm/kg H2O, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular effects of forskolin and phosphodiesterase-III inhibitors

In the first part of this presentation, data is reported on the hemodynamic effects of forskolin given to patients with dilated cardiomyopathy in a concentration of 3 micrograms/kg/min and 4 micrograms/kg/min. At the lower dosage, forskolin had no effect on dP/dtmax, cardiac index, ejection fraction, or myocardial oxygen consumption. With small dosages of dobutamine, however, an increase of all four parameters has been observed in the same group of patients. Systemic vascular resistance and left ventricular enddiastolic pressure fell with forskolin given at the lower concentration. Forskolin administered at a dosage of 4 micrograms/kg/min induced an increase in dP/dtmax by 19% and a 16% rise in heart rate. However, these changes were associated with symptomatic flush syndromes. Therefore, forskolin may serve as a vasodilating substance in lower concentrations, but cannot be used as a positive inotropic compound because of the subjective symptoms. In the second part, a study is reported in which an anti-ischemic effect of the phosphodiesterase inhibitor enoximone was observed in patients with proven significant coronary heart disease. With respect to the hemodynamic parameters, the most striking findings were the decreases in left ventricular enddiastolic pressure and systemic vascular resistance. Furthermore, when left ventricular stroke work index was plotted as a function of the left ventricular enddiastolic pressure, enoximone shifted the left ventricular function curve to the left. Therefore, the anti-ischemic effect of enoximone may not only be due to a reduction in preload and afterload but may rather reflect an effect on diastolic compliance. Studies with intracoronary injections of enoximone and animal experiments support this hypothesis.