Parameters Of Left Ventricular Contractility Research Articles

POSITIVE END-EXPIRATORY PRESSURE DOES NOT COMPROMISE MYOCARDIAL CONTRACTILITY IN MYOCARDIAL ISCHEMIA/REPERFUSION

Therapy for severe myocardial ischemia/reperfusion sometimes necessitates intermittent positive pressure ventilation, which may impair left ventricular function by reduction of ventricular loading. It is unknown today whether positive airway pressure also affects contractile force after myocardial ischemia/reperfusion. The authors tested whether positive end-expiratory pressure (PEEP) impairs myocardial contractility in acute ischemic heart failure. In 11 anesthetized mechanically ventilated pigs (28 +/- 3 kg), cardiac output (CO, aortic flow probe), load-independent parameters of left ventricular contractility (conductance method: preload recruitable stroke work [PRSW] and end-systolic elastance [E(es)]) and preload (end-diastolic volume [EDV] conductance) were assessed before and after myocardial ischemia and reperfusion (left anterior descending artery occlusion, 60 min). Data were taken during PEEP 0, 5, and 10 cm H2O. Before myocardial ischemia, both PEEP 5 and 10 cm H2O reduced CO (P < 0.05) because of a reduction of EDV (P < 0.05, PEEP 10 cm H2O). The PRSW remained unchanged (not significant [NS]) and E(es) increased (P < 0.05, PEEP 10 cm H2O). After myocardial ischemia/reperfusion, CO and PRSW, but not E(es) (NS), deteriorated markedly. At the same time, PEEP 10 cm H2O reduced CO (P < 0.05) and, slightly, EDV (NS). Now, both PRSW (P < 0.05, PEEP 5 cm H2O) and E(es) (P < 0.05, PEEP 10 cm H2O) improved upon ventilation with PEEP. In our model, the administration of PEEP impaired global left ventricular function before and after myocardial ischemia/reperfusion. The observed impairment is not attributable to compromised contractility.

A novel approach to maintaining cardiovascular stability after hemorrhagic shock: Beneficial effects of adrenomedullin and its binding protein

Vascular responsiveness to adrenomedullin (AM), a recently discovered vasodilator peptide, is depressed after hemorrhage and resuscitation. Downregulation of AM binding protein-1 (ie, AMBP-1) appears to be responsible for this hyporesponsiveness. Therefore, we hypothesize that administration of AM/AMBP-1 improves cardiovascular responses after hemorrhagic shock and resuscitation. Male rats were bled to and maintained at a mean blood pressure of 40 mm Hg for 90 minutes. The animals were then resuscitated with 4 times the volume of shed blood with Ringer's lactate over 60 minutes. At 15 minutes after the beginning of resuscitation in hemorrhaged animals, AM alone, AMBP-1 alone, AM in combination with AMBP-1, or vehicle (phosphate-buffered saline solution) was administered intravenously over 45 minutes. At 4-hour postresuscitation, in vivo left ventricular contractility parameters, maximal rates of ventricular pressure increase (+dP/dt max ) and decrease (-dP/dt max ), were determined. Cardiac output and organ blood flow were measured with the use of radioactive microspheres. In an additional group of animals, cardiac tumor necrosis factor-alpha (TNF-alpha) levels were measured by an enzyme-linked immunosorbent assay. Four hours after resuscitation, +dP/dt max , -dP/dt max , cardiac output, and organ blood flow in the liver, small intestine, and kidneys were decreased while treatment with AM/AMBP-1 increased these parameters ( P < .05). Moreover, cardiac TNF-alpha levels were elevated at 4 hours after hemorrhage and resuscitation, while AM/AMBP-1 treatment reduced them to sham levels ( P < .05). Administration of AM/AMBP-1 appears to be a useful approach for restoring and maintaining cardiovascular stability after severe hemorrhagic shock and crystalloid resuscitation.

Impairment of coronary flow reserve and left ventricular function in the brain-dead canine heart

The mechanisms of cardiac dysfunction after brain death, which are thought to be mainly associated with massive catecholamine release, have not been fully elucidated, especially with respect to the coronary circulation. The aim of this study was to investigate the changes in function of the coronary artery and its contribution to hemodynamic deterioration in a canine brain death model. Brain death was induced by rapid inflation of a subdurally placed balloon catheter. Hemodynamic measurements including assessment of left ventricular contractility using pressure-volume relations and biochemical analyses of blood samples were performed in seven dogs. Coronary flow reserve in the same brain death model was assessed by changes in coronary flow and resistance induced by administering a vasodilator directly into the coronary artery in another eight dogs. A hyperdynamic response was transiently observed after induction of brain death, followed by decreases in arterial pressure, cardiac output, and coronary blood flow. Parameters of left ventricular contractility as measured by pressure-volume relations had significantly deteriorated by 60 min after brain death. Percent changes in coronary flow by administration of acetylcholine and sodium nitroprusside were 272 and 209%, respectively, before brain death; these were decreased to 178 and 145% at 30 min after brain death, and to 192 and 153% at 60 min. Coronary resistance ratios were also significantly increased at 30 and 60 min after brain death. Impairment of coronary flow reserve was found in the brain-dead canine heart. This impaired coronary circulation may constitute a disadvantage of prevention and recovery of cardiac dysfunction after induction of brain death.

Effects of sildenafil on myocardial infarct size, microvascular function, and acute ischemic left ventricular dilation.

Adverse cardiac events in patients treated with the phosphodiesterase-5 inhibitor sildenafil for erectile dysfunction raised concerns about its safety in ischemic heart disease. In anesthetized open-chest rabbits, receiving 1.45 mg/kg sildenafil intravenously or saline 30 min prior to ischemia (n=12, each), infarct size (IS, triphenyltetrazolium), the area of no-reflow (ANR, thioflavin S) (% of the risk area, RA, blue dye), and regional myocardial blood flow (RMBF, radioactive microspheres) were measured after 30 min of coronary occlusion and 180 min of reperfusion. Left ventricular hemodynamics and dimensions (echocardiography) were determined in a separate series of animals (n=5, each). Sildenafil significantly lowered arterial blood pressure before occlusion (-17 to -19 mmHg over 30 min), but during ischemia and reperfusion hemodynamics were comparable to controls. IS in treated animals (51+/-4%) did not significantly differ from control animals (47+/-4%). No major arrhythmias or lengthening of QT/QTc occurred. While sildenafil slightly increased RMBF and significantly reduced specific vascular resistance in the RA during reperfusion (51+/-7 versus 73+/-10 mmHg g min/ml, P<0.05), the ANR (46+/-3%) was similar to control animals (44+/-4%). Sildenafil reduced left ventricular dP/dt(max) (P<0.05) and dP/dt(min) (P<0.01) in non-ischemic conditions, and slightly during ischemia, along with a pronounced decrease in ischemic left ventricular end-diastolic pressure (9+/-2 versus 15+/-2 mmHg after saline, P<0.05), but did not attenuate acute ischemic left ventricular dilation. Sildenafil reduced cardiac pre- and afterload, and parameters of left ventricular contractility. Myocardial necrosis and microvascular dysfunction were neither exacerbated nor attenuated.

Continuous resuscitation after hemorrhage and acute fluid replacement improves cardiovascular responses*

Background. Although acute fluid replacement after trauma and severe hemorrhage remains the cornerstone in the management of trauma victims, it remains unknown whether continuous resuscitation after trauma-hemorrhage and acute fluid replacement produces salutary effects on cardiovascular function and reduces proinflammatory cytokine release. Methods. Adult male rats underwent laparotomy (ie, soft tissue trauma) and were bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of the shed blood volume was returned in the form of Ringer's lactate (RL). The animals were then resuscitated with 4 times the volume of shed blood with RL for 60 minutes, followed by continuous resuscitation with RL at 5 mL/h/kg for 48 hours after the acute fluid replacement. At 48 hours after hemorrhage, mean arterial pressure, cardiac output, and left ventricular contractility parameters, such as the maximal rates of ventricular pressure increase (+dP/dtmax) and decrease (−dP/dtmax), were determined. Microvascular blood flow in the intestine and kidney was assessed by laser Doppler flowmetry. In addition, plasma levels of TNF-α were assayed by enzyme-linked immunosorbent assay. Results. The mean arterial pressure and cardiac output were decreased by 34% and 18%, respectively, at 48 hours after hemorrhage and acute resuscitation. Continuous resuscitation, however, markedly improved these parameters. Similarly, +dP/dtmax and −dP/dtmax decreased significantly after hemorrhage and acute fluid replacement but was restored to sham values after continuous resuscitation. Microvascular blood flow in the gut and kidneys was decreased after hemorrhage and acute resuscitation by 34% and 35%, respectively. However, intestinal and renal perfusion was maintained at the sham levels at 48 hours after continuous resuscitation. In addition, the upregulated TNF-α after acute resuscitation alone was reduced after continuous resuscitation. Conclusions. Continuous resuscitation after acute fluid replacement appears to be a useful approach for restoring and maintaining cardiovascular function and organ perfusion after trauma and severe hemorrhage.(Surgery 2001;129:559-66.)

The Effect of Sudden Failure of a Rotary Blood Pump on Left Ventricular Performance in Normal and Failing Hearts

We investigated the hemodynamic effect of regurgitation (or back-flow) due to sudden failure of a rotary blood pump (diagonal pump). Seven healthy sheep (Group C) and 7 with chronic heart failure (Group F) were studied. Chronic heart failure was obtained by intracoronary injection of microspheres several weeks earlier. Left ventricular function and ventricular efficacy were assessed by the pressure-volume relationship. The back-flow through the stopped pump was significantly lower in Group F (2.3 +/- 0.34 L/min) than in Group C (2.8 +/- 0.33 L/min). Mean aortic blood pressure dropped significantly from 68.3 +/- 9.65 to 61.9 +/- 9.75 mm Hg in Group C and from 62.5 +/- 9.12 to 51.5 +/- 9.08 in Group F but remained stable during the 15 min period of pump stop. Parameters of left ventricular contractility (preload recruitable stroke work) dropped significantly in both groups, remained stable during the pump stop, and returned to baseline values 30 min after the end of back-flow. The ventricular efficacy (in terms of energy transfer) was tolerant against this acute volume overload even in the failing hearts. Sudden pump failure of a rotary blood pump leads to an acute depression of the hemodynamic state and myocardial contractility. However, this depression remained stable over 15 min, did not lead to further deterioration of the animals, and was completely reversible.

Cardiac contractility and structure are not significantly compromised even during the late, hypodynamic stage of sepsis.

Although cardiac function is depressed during endotoxic shock, it remains controversial whether the ventricular contractility and structure are altered during sepsis. To resolve this issue, rats were subjected to polymicrobial sepsis by cecal ligation and puncture (CLP). At 2, 5, and 10 h after CLP (i.e., the early, hyperdynamic stage of sepsis) or 20 h after CLP (the late, hypodynamic stage of sepsis, based on the depressed tissue perfusion), in vivo left ventricular contractility parameters such as maximal rate of the left ventricular pressure increase (+dP/dtmax) and decrease (-dP/dtmax), maximal rate of "pressure-normalized" change in ventricular pressure (dP/dtmax/P), and ventricular peak systemic pressure were determined using a Digi-Med Heart Performance Analyzer. In additional groups of animals, ultrastructure of the cardiac muscle in the left ventricle was examined at 5, 10, or 20 h after CLP, using a transmission electron microscope. The results indicate that +dP/dtmax and dP/dtmax/P increased significantly at 2-10 h after CLP. The values of -dP/dtmax and ventricular peak systemic pressure increased significantly at 2 and 5 h after the onset of sepsis, respectively. These in vivo ventricular contractility parameters, however, were not significantly different from shams at 20 h after CLP. Ultrastructural examination showed that enlarged T-tubules were prominent during the hyperdynamic stage of sepsis, which was correlated with the increased cardiac contractility. Although focal and moderate hypertrophy as well as expanded intermyocyte junctions could be observed occasionally, myocardial cells did not appear to be compromised at 20 h after CLP. Thus, the transition from the hyperdynamic to hypodynamic circulation during sepsis does not appear to be due to any depression in myocardial function because cardiac contractility and structure are not compromised even during the late, hypodynamic stage of sepsis. However, further investigation is required to determine whether cardiac function is depressed at the terminal stage of polymicrobial sepsis.

The relative phospholamban and SERCA2 ratio: a critical determinant of myocardial contractility.

Phospholamban is a regulatory phosphoprotein which modulates the active transport of Ca2+ by the cardiac sarcoplasmic reticular Ca(2+)-ATPase enzyme (SERCA2) into the lumen of the sarcoplasmic reticulum. Phospholamban, which is a reversible inhibitor of SERCA2, represses the enzyme's activity, and this inhibition is relieved upon phosphorylation of phospholamban in response to beta-adrenergic stimulation. In this way, phospholamban is an important regulator of SERCA2-mediated myocardial relaxation during diastole. This report centers on the hypothesis that the relative levels of phospholamban: SERCA2 in cardiac muscle plays an important role in the muscle's overall contractility status. This hypothesis was tested by comparing the contractile parameters of: a) murine atrial and ventricular muscles, which differentially express phospholamban, and b) murine wild-type and phospholamban knock-out hearts. These comparisons revealed that atrial muscles, which have a 4.2-fold lower phospholamban: SERCA2 ratio than ventricular muscles, exhibited rates of force development and relaxation of tension, which were three-fold faster that these parameters for ventricular muscles. Similar comparisons were made via analyses of left-ventricular pressure development recorded for isolated, work-performing hearts from wild-type and phospholamban knock-out mice. In these studies, hearts from phospholamban knock-out mice, which were devoid of phospholamban, exhibited enhanced parameters of left-ventricular contractility in comparison to wild-type hearts. These results suggest that the relative phospholamban: SERCA2 ratio is critical in the regulation of myocardial contractility and alterations in this ratio may contribute to the functional deterioration observed during heart failure.

Influence of nimodipine on cardiovascular parameters during coronary surgery.

A total of 78 patients about to undergo open-heart surgery (ACVB) were given nimodipine, a new calcium antagonist, in different doses (0.5 or 1.0 microgram/kg body weight min or 0.03/0.06 mg/kg h) before and during extracorporeal circulation. During infusion (10 to 40 min), the hemodynamic parameters were recorded, including intrapulmonary pressures, the cardiac output and the left ventricular contractility parameters LVP and dp/dtmax. The administration of nimodipine resulted in a dose-dependent reduction of the pulmonary and peripheral vascular resistance with a subsequent decrease of the mean arterial pressure or perfusion pressure (during extracorporeal circulation). The left ventricular pressure (LVP) was reduced, whereas sometimes the cardiac output increased considerably. The contractility (dp/dtmax) was not impaired even by the high nimodipine dose. The heart rate, too, remained unaffected. The nimodipine dose of 0.5 microgram/kg min used in neurosurgery for therapy did not cause any clinically relevant decrease in blood pressure; at higher doses (greater than or equal to 1.0 microgram/kg min) an excessive fall of the diastolic pressure must be avoided in patients with severe (coronary) sclerosis, because a reduced perfusion of poorly vascularized myocardial regions can occur despite improved global perfusion.

Anatomic correction of transposition of the great arteries associated with ventricular septal defect: midterm results in 50 patients.

From May 1977 to August 1982 50 patients who were 1.5 to 44 months old underwent anatomic correction of transposition of the great arteries (TGA) and closure of ventricular septal defect (VSD) at our institution. Thirty-nine patients underwent preliminary pulmonary arterial banding. Hospital mortality was 32%: four patients died as a result of technical problems, seven as a result of associated lesions, three of pulmonary hypertension, and two of left ventricular failure. Three other patients died after the first postoperative month (one of mediastinitis, one at reoperation for a residual VSD, and one of pulmonary hypertension). All 31 survivors are in excellent clinical condition and are in sinus rhythm after a mean follow-up period of 31 +/- 14 months. Twenty-five patients were reinvestigated by echocardiography (M mode and two-dimensional) and/or catheterization. Parameters of left ventricular contractility were within normal limits, but systolic aortic diameter was larger than normal (p less than .01). Seven patients had stenosis of the right ventricular outflow tract and five of these required reoperation. The two persistent problems with the anatomic correction of TGA associated with VSD are a relatively high operative mortality and secondary right outflow tract stenosis. However, use of this procedure results in better left ventricular function and fewer arrhythmias than does use of atrial repair techniques and also results in the use of the anatomically left ventricle as the systemic ventricle.

Echocardiographic LV function in thyrotoxicosis

Serial echocardiographic studies were made in 11 patients with thyrotoxicosis. In the untreated thyrotoxic state heart rate was increased (96 ± 14 (SD) beats/minute) as were measurements of left ventricular (LV) contractility. LV shortening fraction was 40 ± 6 per cent (mean ± SD), mean velocity of circumferential fiber shortening was 1.60 ± 0.32 circumferences/sec., and velocity of posterior wall motion 71 ± 13 mm./sec. Stroke index and cardiac index were increased: 52 ± 18 (SD) ml./beat per M. 2 and 5.0 ± 1.8 (SD) liter/minute per M. 2, respectively. Cardiac chamber size was normal in all but one very ill patient and did not change during the study. Treatment with propranolol, 60 mg./day, produced a dramatic and immediate improvement in the clinical state of the patient. Heart rate decreased to 84 ± 11 beats/minute (p < 0.01), stroke index increased marginally (p > 0.05), and cardiac index was unaltered (p > 0.05). There was no change in parameters of LV contractility (p > 0.05). Treatment with a specific antithyroid drug (methimazole or propylthiouracil) brought about further improvement in the clinical state and a further decrease in heart rate (p < 0.01). LV contractility decreased and after two to three months, when the patients were euthyroid, these measurements were in the range of normal (per cent shortening of the LV diameter 37 ± 4, p < 0.01; mean velocity of circumferential fiber shortening 1.31 ± 0.23 circumferences/sec., p < 0.05; maximum velocity of posterior wall motion, 46 ± 14 mm./sec., p < 0.01). Systolic time interval measurements were in keeping with these data. They showed enhanced LV performance in the control state, no change with propranolol, and they returned toward the range of normal after definitive antithyroid treatment.