Metabolism of the perfused rabbit heart. V. Verapamil-induced release of creatine kinase

1982 ◽  
Vol 60 (7) ◽  
pp. 952-959 ◽  
Author(s):  
Miguel A. Chiong
Keyword(s):  
Creatine Kinase ◽  
Adenine Nucleotides ◽  
Systolic Pressure ◽  
Creatine Phosphate ◽  
Rabbit Heart ◽  
Left Ventricular ◽  
Calcium Stores ◽  
Ventricular Performance ◽  
Permeability Characteristics ◽  
Energy Stores

The effects of verapamil (VER), at concentrations of 0, 10−9, 10−8, 10−7, and 5 × 10−7 M (or 0, 0.5, 5, 50, and 250 ng/mL) were studied in the isolated rabbit heart during 70 min of aerobic perfusion with a standard Krebs–bicarbonate medium at 37 °C. The studied variables were left ventricular performance (RPP, heart rate times left ventricular (LV) systolic pressure), coronary sinus flow (CSF), oxygen uptake [Formula: see text], rate of creatine kinase (CK) release, and energy stores (glycogen, creatine phosphate (CP), ATP, and total adenine nucleotides (TAN)).The results show that (i) VER depressed RPP in a dose-related manner; (ii) [Formula: see text] declined as VER concentration increased except in the 5 × 10−7 M group which showed a paradoxical increase in O2 uptake; (iii) CSF was only slightly decreased by VER with the exception of the 5 × 10−7 M group, which showed an increase in flow; (iv) VER was associated with increments in the rates of CK release in a dose-related fashion (2, 4, 15, and 29 times the rate observed in the untreated group), and (v) VER was associated with slight decrease in glycogen levels, but no changes in CP or adenine nucleotides.It is concluded that, in our preparation, VER caused marked increases in the rate of CK loss in the absence of depletion of total energy stores. The data suggest that the drug affects the permeability characteristics of the sarcolemma, perhaps via localized depletion of calcium stores.

Low extracellular Ca2+ and enzyme release in the perfused rabbit heart

1984 ◽  
Vol 62 (9) ◽  
pp. 1158-1165 ◽  
Author(s):  
Pierre A. Fortier ◽  
Gary K. Bedford ◽  
Miguel A. Chiong
Keyword(s):  
Creatine Kinase ◽  
Systolic Pressure ◽  
Rabbit Heart ◽  
Left Ventricular ◽  
Control Group ◽  
Enzyme Release ◽  
Ventricular Systolic Pressure ◽  
Coronary Sinus Flow ◽  
Perfused Rabbit Heart ◽  
Cardiac Functions

Previous studies have shown that the well-oxygenated perfused rabbit heart releases creatine kinase when treated with the calcium antagonist drug verapamil (VER) in a dose-related manner. It is possible that this effect is related to Ca2+ ion deprivation of the sarcolemma. This possibility was explored by perfusing hearts with low Ca2+ (0.5, 0.23, 0.15, and 0 mM) versus a control group (1.27 mM Ca2+) for 60 min. Low Ca2+ perfusion was associated with (i) reduction in the heart rate – left ventricular systolic pressure product and O2 consumption, (ii) tendency for the coronary sinus flow to increase, (iii) electromechanical dissociation, prolongation of atrioventricular conduction and QT interval, and (iv) decrease in myocardial glycogen. Lower total adenosine nucleotides were found only in the 0 mM Ca2+ group. As the Ca2+ concentration was reduced, the hearts lost increasing amounts of creatine kinase, aspartate aminotransferase, and lactate dehydrogenase. These results confirm the importance of Ca2+ ions in contractile and electrical cardiac functions and show that decreased availability of this cation leads to increasing enzyme leakage resembling that seen in VER-treated hearts.

Metabolism of the isolated perfused rabbit heart. III. Energy stores and creatine kinase release during prolonged reoxygenation and atrial pacing

1979 ◽  
Vol 57 (10) ◽  
pp. 1058-1066 ◽  
Author(s):  
Miguel A. Chiong ◽  
Timothy L. Winton
Keyword(s):  
Creatine Kinase ◽  
Mechanical Performance ◽  
Recovery Period ◽  
Systolic Pressure ◽  
Rabbit Heart ◽  
Left Ventricular ◽  
Atrial Pacing ◽  
Myocardial Uptake ◽  
Ventricular Systolic Pressure ◽  
Perfused Rabbit Heart

When the perfused rabbit heart is reoxygenated for 75 min after 25 min of anoxic perfusion, left ventricle performance stabilizes at 50% of control levels, but the rate of creatine kinase (CK) release is high (1.9 U/min) and ATP stores are low (5 μmol/g dry weight). These results suggest that the preparation is on the verge of severe failure. This possibility was investigated by following the recovery for an extra 60 min of reoxygenation and by stressing the hearts with atrial pacing.The data show that no deterioration occurred during the extra recovery period; on the contrary, mechanical performance remained stable, while the rate of CK release fell to 1.1 U/min, and ATP stores increased by 204%. In aerobic hearts, pacing increased the product of left ventricular systolic pressure (LVSP) and heart rate, myocardial uptake of oxygen [Formula: see text], coronary sinus flow, and O2 extraction, but LVSP and [Formula: see text] per beat fell. Similar responses were seen in postanoxic hearts, but LVSP improved during pacing while the rate of CK loss declined and ATP stores increased. These metabolic changes were inversely related to the rate of contraction. It is concluded that the preparation was not deteriorating at 75 min of reoxygenation, and that its metabolism was improved by cardiac pacing.

Metabolism of the perfused rabbit heart. IV. Effects of β-adrenergic blockade on enzyme release and late energy stores during postanoxic reoxygenation

1980 ◽  
Vol 58 (5) ◽  
pp. 469-476 ◽  
Author(s):  
Miguel A. Chiong ◽  
Henry Stefaniszyn
Keyword(s):  
Heart Rate ◽  
Energy Charge ◽  
Systolic Pressure ◽  
Rabbit Heart ◽  
Left Ventricular ◽  
Adrenergic Blockade ◽  
Enzyme Release ◽  
Ventricular Systolic Pressure ◽  
Energy Stores ◽  
Left Ventricular Systolic Pressure

The effects of 80 μM dl-propranolol on left ventricular (LV) performance, energy stores, and creatine kinase (CK) release were studied in a modified Langendorff rabbit heart preparation during 75 min of aerobic perfusion and postanoxic reoxygenation.The data showed that this concentration of propranolol, which blocked the effects of β-adrenergic stimulation without affecting LV performance, coronary sinus flow (CSF), or oxygen consumption [Formula: see text], was associated with greater stores of glycogen and adenine nucleotides at the end of aerobic perfusion. Similar effects were observed during postanoxic reoxygenation, when recoveries of left ventricular systolic pressure, heart rate, heart rate - left ventricular systolic pressure product, CSF, and [Formula: see text] remained unchanged during propranolol administration, but myocardial concentrations of glycogen, creatine phosphate, and ATP were greater and the ATP:AMP ratio and the energy charge were higher than in untreated hearts. In addition, the rate of CK loss was lower in the blocked postanoxic hearts than in the unblocked group. These results indicate that propranolol had a beneficial effect on cardiac metabolism during postanoxic recovery tending to normalize energy stores and to reduce enzyme loss during reoxygenation of perfused rabbit hearts without affecting mechanical performance, coronary flow, or O2 metabolism.

Chronic infarction decreases maximum cardiac work and sensitivity of heart to extracellular calcium

1985 ◽  
Vol 249 (1) ◽  
pp. H80-H87 ◽  
Author(s):  
E. Fellenius ◽  
C. A. Hansen ◽  
O. Mjos ◽  
J. R. Neely
Keyword(s):  
Adenine Nucleotides ◽  
Creatine Phosphate ◽  
Scar Tissue ◽  
Left Ventricular ◽  
Compensatory Hypertrophy ◽  
Tissue Mass ◽  
Pressure Development ◽  
Whole Heart

Rat hearts were infarcted in vivo by ligation of the left ventricular coronary artery to cause an initial 40% loss of viable tissue by weight. Due to compensatory hypertrophy of the surviving myocardium and progression of the infarct to scar tissue, the infarct represented approximately 25% by weight of the whole heart after 1 wk. After 1 or 3 wk, these infarcted hearts were removed and perfused in vitro by the working hearts technique. Ventricular pressure development and positive dP/dt were lower in infarcted hearts compared with sham-operated ones. O2 consumption and glucose utilization by viable tissue per unit pressure development was the same in normal and infarcted hearts. Levels of creatine phosphate and free creatine were decreased, but ATP and total adenine nucleotides were well maintained. The inotropic response to decreases in extracellular [Ca2+] was much greater in infarcted hearts than in sham controls. Prenalterol increased ventricular function proportionally more in infarcted than in the sham-operated hearts, suggesting that down regulation of beta receptors was not a problem. The infarcted hearts were much more sensitive to verapamil than control hearts. It is concluded that the depressed function of the noninfarcted tissue of chronically infarcted hearts is due in part to loss of functioning tissue mass and in part to decreased sensitivity to extracellular Ca2+.

Ventricular performance, pressure-volume relationships, and O2 consumption during hypothermia

1964 ◽  
Vol 206 (1) ◽  
pp. 67-73 ◽  
Author(s):  
R. G. Monroe ◽  
R. H. Strang ◽  
C. G. LaFarge ◽  
J. Levy
Keyword(s):  
Peak Pressure ◽  
Diastolic Pressure ◽  
Isolated Heart ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Ventricular Performance ◽  
Heart Rates ◽  
Performance Pressure ◽  
Air Chamber ◽  
Lower Temperature

Left ventricular performance in the isolated heart of a dog was observed at normal temperatures (37.7 C) and under hypothermia (32.2 C) at comparable heart rates. The peak pressure of isovolumic contractions at the same ventricular end-diastolic pressures averaged 40% higher at the lower temperature. Diastolic pressure-volume relationships were similar at both temperatures. In studies in which the ventricle ejected fluid and performed work the hypothermic ventricle was capable of performing greater work at comparable heart rates, left ventricular end-diastolic pressures, and loading. When the ventricle was allowed to perform work by compressing air into a chamber of constant volume left ventricular oxygen consumption (Vo2) increased with the peak systolic pressure as the temperature was lowered. If the peak systolic pressure was maintained constant by increasing the volume of the air chamber as the temperature was lowered no consistent relationship could be shown between left ventricular Vo2 and the integral of systolic pressure in time which invariably increased with hypothermia.

Crystalloid and perfluorochemical perfusates in an isolated working rabbit heart preparation

1985 ◽  
Vol 249 (2) ◽  
pp. H285-H292 ◽  
Author(s):  
J. M. Chemnitius ◽  
W. Burger ◽  
R. J. Bing
Keyword(s):  
Cardiac Output ◽  
Coronary Flow ◽  
Systolic Pressure ◽  
Pressure Rise ◽  
Rabbit Heart ◽  
Left Ventricular ◽  
Heart Weight ◽  
Perfused Heart ◽  
Heart Preparation ◽  
Perfused Hearts

Krebs-Henseleit buffer (KH) and a perfluorochemical (FC-43) were compared as perfusates in an isolated working rabbit heart preparation. Both perfusates were oxygenated in an identical manner using an infant bubble oxygenator. After 60 min of perfusion, no difference could be detected in the ratio of wet to dry heart weight between KH- and FC-43-perfused hearts (KH, 6.25 +/- 0.3; FC-43, 5.99 +/- 0.20). Left ventricular systolic pressure, maximal rate of left ventricular pressure rise, mean aortic systolic pressure, cardiac output, aortic flow, left ventricular power, and myocardial O2 consumption (MVO2) were significantly higher in FC-43-perfused hearts throughout the time of perfusion. However, there were no differences in resistance to cardiac output and heart rate. In KH- and FC-43-perfused hearts, MVO2 and left ventricular power were closely correlated (KH, r = 0.793; FC-43, r = 0.831). Significantly higher coronary flow of KH-perfused hearts could be attributed to the lower viscosity of KH (1.05 Pa . s) compared with FC-43 (1.91 Pa . s). Increased O2 extraction during KH perfusion could not compensate for low O2-carrying capacity of KH buffer (345 compared with 705 nmol O2 X ml-1 in FC-43 emulsion). A postischemic increase of coronary flow was observed only in FC-43-perfused hearts (28%). These results demonstrate a different response of perfused heart preparations to FC-43 and KH buffer.

Effect of vasopressin on left ventricular performance

1993 ◽  
Vol 264 (1) ◽  
pp. H53-H60
Author(s):  
C. P. Cheng ◽  
Y. Igarashi ◽  
H. S. Klopfenstein ◽  
R. J. Applegate ◽  
Z. Shihabi ◽  
...  
Keyword(s):  
Systolic Pressure ◽  
Left Ventricular ◽  
Systemic Resistance ◽  
Stroke Work ◽  
Arterial Elastance ◽  
Ventricular Performance ◽  
Systolic Volume ◽  
End Diastolic Volume ◽  
End Systolic Volume ◽  
The Right

We assessed the effect of arginine vasopressin (AVP) on left ventricular (LV) performance in eight conscious dogs. Five minutes after AVP infusion (6 microns.kg-1 x min-1 for 2 min) the plasma AVP was elevated from 3.9 +/- 0.9 to 14.7 +/- 4.6 pg/ml (P < 0.05). With all reflexes intact, AVP caused significant increases in LV end-systolic pressure (P) (112 +/- 8 vs. 122 +/- 7 mmHg, P < 0.05) end-systolic volume (V) (30 +/- 5.8 vs. 38 +/- 7.7 ml, P < 0.05), total systemic resistance (6.2 +/- 1.8 vs. 10.6 +/- 4.0 mmHg.dl-1 x min, P < 0.01) and arterial elastance (Ea) (6.8 +/- 3.0 vs. 8.6 +/- 3.9 mmHg/ml, P < 0.05), while the heart rate (110 +/- 6 vs. 82 +/- 10 beats/min, P < 0.05) and stroke volume (16.5 +/- 4.3 vs. 14.2 +/- 3.9 ml, P < 0.05) were decreased. There was no significant change in the coronary sinus blood flow (82 +/- 19 vs. 78 +/- 22 ml/min, P = not significant). AVP decreased the slopes of LV end-systolic P-V relation (10.7 +/- 1.1 vs. 8.1 +/- 1.9 mmHg/ml, P < 0.05), the maximal first derivative of LV pressure (dP/dtmax)-end-diastolic volume (VED) relation (135.2 +/- 18.7 vs. 63.1 +/- 7.7 mmHg.s-1 x ml-1, P < 0.05), and the stroke work-VED relation (81.1 +/- 4.1 vs. 66.7 +/- 2.8 mmHg, P < 0.05) and shifted the relations to the right, indicating a depression of LV performance. A similar increase in Ea produced by methoxamine did not depress LV performance.(ABSTRACT TRUNCATED AT 250 WORDS)

Nonlinearity of indexes of left ventricular performance: effects on estimation of slope and diameter axis intercepts

1991 ◽  
Vol 260 (6) ◽  
pp. H1802-H1809
Author(s):  
C. F. Toombs ◽  
J. Vinten-Johansen ◽  
H. Yokoyama ◽  
W. E. Johnston ◽  
J. S. Julian ◽  
...  
Keyword(s):  
Systolic Pressure ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Accurate Estimation ◽  
Stroke Work ◽  
Left Ventricular Performance ◽  
Ventricular Performance ◽  
Wide Range ◽  
Performance Effects ◽  
Linear Fit

The slope and diameter axis intercept (D0) of the linear indexes end-systolic pressure-diameter relation (ESPDR), maximum of the first derivative of left ventricular pressure (dP/dtmax)-end-diastolic diameter relation (dP/dtmax-Ded), and dimensional preload-recruitable stroke work relation (PRDSW) are used to describe left ventricular performance. We tested the hypothesis that nonlinearity in these indexes would preclude accurate estimation of slope and D0. In nine pentobarbital-anesthetized dogs, right heart bypass was used to obtain a wide range of pressure-minor axis diameter (sonomicrometry) points from which the three indexes were derived. For ESPDR and dP/dtmax-Ded, a nonlinear fit (y = ax2 + bx + c) approximated the data better than a linear fit, with significant nonlinearity toward the diameter axis (a = -10.28 +/- 3.42 and -111.2 +/- 26.2, respectively, P less than 0.05). Although linear D0 was significantly less than nonlinear D0, this difference was overcome by the diameter intercept at a midrange value of end-systolic pressure or dP/dtmax. PRDSW demonstrated no significant nonlinearity (a = -4.40 +/- 3.53, P = 0.86) but extrapolation to D0 demonstrated linear and nonlinear differences. We conclude that 1) ESPDR and dP/dtmax-Ded demonstrate significant nonlinearity, while PRDSW is well-approximated by a linear fit over a large range of data points; and 2) extrapolation of D0 is inaccurate in all three indexes, while a midrange intercept is independent of the model used to fit the data. Left ventricular performance may be more accurately described by linear slope and midrange diameter intercept over comparable ranges of data.

Effects of ventricular pacing on regional left ventricular performance in the dog

1980 ◽  
Vol 238 (6) ◽  
pp. H858-H867 ◽  
Author(s):  
F. R. Badke ◽  
P. Boinay ◽  
J. W. Covell
Keyword(s):  
Myocardial Function ◽  
Systolic Pressure ◽  
Lateral Wall ◽  
Left Ventricular ◽  
Atrial Pacing ◽  
Ventricular Pacing ◽  
Regional Myocardial Function ◽  
Ventricular Performance ◽  
Reciprocal Interaction ◽  
Anesthetized Dogs

Changes in regional left ventricular (LV) performance induced by ventricular pacing were studied in two groups of open-chest anesthetized dogs. In the first group of five dogs, local function at the LV anterior base, anterior apex, and posterior apex was assessed by ultrasonic crystal pairs with atrial, right ventricular, LV apical, and LV base pacing. Ventricular pacing produced asynchrony of contraction and marked changes in the shortening pattern at each site, as well as an average 27% reduction in peak systolic pressure and peak dP/dt compared to atrial pacing. Moreover, the extent of shortening during LV ejection was reduced or unchanged at all sites measured during ventricular pacing. In the second group of five dogs, function of the septum and opposing LV lateral wall was studied with atrial and LV lateral wall pacing. Lateral function was assessed with a crystal pair and septal function by cineradiography of a lead bead implanted in the septum. Ventricular pacing produced reciprocal interaction between the two walls, with early lateral shortening inducing septal bulging and late septal shortening inducing lateral wall systolic lengthening. We conclude that ventricular pacing produces significant changes in regional myocardial function, likely induced by reciprocal interaction of opposing myocardial regions. Furthermore, such interaction appears deleterious to global ventricular function, presumably because volume is sequestered and pressure is dissipated into relatively inactive segments that are out of phase with the bulk of contracting myocardium.

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