Hypertonic saline is a negative inotropic agent in normovolumic dogs

1994 ◽  
Vol 267 (2) ◽  
pp. H667-H677 ◽  
Author(s):  
P. D. Constable ◽  
W. W. Muir ◽  
P. F. Binkley
Keyword(s):  
Cardiac Output ◽  
Hypertonic Saline ◽  
Diastolic Pressure ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Rate Of Change ◽  
Inotropic Agent ◽  
Inotropic Effects ◽  
End Diastolic Volume

The inotropic effects of hypertonic saline (HS) and hyperosmotic dextrose (HD; 2,400 mosmol/l, 4 ml/kg) were determined in normovolumic, chloralose-anesthetized, intact (n = 14) and autonomically blocked (n = 8) dogs. Solutions were infused intravenously over 3 min. HS and HD rapidly increased preload in both intact and autonomically blocked dogs, as assessed by significant (P < 0.05) increases in plasma volume, end-diastolic volume, and end-diastolic pressure. In intact dogs, HS produced a nonsignificant decrease in end-systolic elastance (Ees) and a nonsignificant increase in the maximal rate of change of left ventricular pressure (dP/dtmax) and cardiac output, whereas HD produced a significant increase in Ees, dP/dtmax, and cardiac output. In autonomically blocked dogs, HS significantly decreased Ees and significantly increased dP/dtmax but did not alter cardiac output, whereas HD significantly increased Ees, dP/dtmax, and cardiac output. We conclude that in normovolumic animals, HS is a negative inotropic agent, HD is a positive inotropic agent, and the in vivo effect of an ionic hyperosmotic agent (HS) differs from that of a nonionic hyperosmotic agent (HD).

Role of impaired myocardial relaxation in the production of elevated left ventricular filling pressure

2005 ◽  
Vol 288 (3) ◽  
pp. H1203-H1208 ◽  
Author(s):  
Ilan Hay ◽  
Jonathan Rich ◽  
Paul Ferber ◽  
Daniel Burkhoff ◽  
Mathew S. Maurer
Keyword(s):  
Heart Failure ◽  
Heart Rate ◽  
Cardiac Output ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Myocardial Relaxation ◽  
End Diastolic Volume ◽  
Wide Range

Although present in many patients with heart failure and a normal ejection fraction, the role of isolated impairments in active myocardial relaxation in the genesis of elevated filling pressures is not well characterized. Because of difficulties in determining the effect of prolonged myocardial relaxation in vivo, we used a cardiovascular simulated computer model. The effect of myocardial relaxation, as assessed by τ (exponential time constant of relaxation), on pulmonary vein pressure (PVP) and left ventricular end-diastolic pressure (LVEDP) was investigated over a wide range of τ values (20–100 ms) and heart rate (60–140 beats/min) while keeping end-diastolic volume constant. Cardiac output was recorded over a wide range of τ and heart rate while keeping PVP constant. The effect of systolic intervals was investigated by changing time to end systole at the same heart rate. At a heart rate of 60 beats/min, increases in τ from a baseline to extreme value of 100 ms cause only a minor increase in PVP of 3 mmHg. In contrast, at 120 beats/min, the same increase in τ increases PVP by 23 mmHg. An increase in filling pressures at high heart rates was attributable to incomplete relaxation. The PVP-LVEDP gradient was not constant and increased with increasing τ and heart rate. Prolonged systolic intervals augmented the effects of τ on PVP. Impaired myocardial relaxation is an important determinant of PVP and cardiac output only during rapid heart rate and especially when combined with prolonged systolic intervals. These findings clarify the role of myocardial relaxation in the pathogenesis of elevated filling pressures characteristic of heart failure.

In vivo murine left ventricular pressure-volume relations by miniaturized conductance micromanometry

1998 ◽  
Vol 274 (4) ◽  
pp. H1416-H1422 ◽  
Author(s):  
Dimitrios Georgakopoulos ◽  
Wayne A. Mitzner ◽  
Chen-Huan Chen ◽  
Barry J. Byrne ◽  
Huntly D. Millar ◽  
...  
Keyword(s):  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Genetically Engineered ◽  
Ventricular Pressure ◽  
Stroke Work ◽  
Time Varying ◽  
End Diastolic Volume ◽  
Novel Approach ◽  
Preload Reduction

The mouse is the species of choice for creating genetically engineered models of human disease. To study detailed systolic and diastolic left ventricular (LV) chamber mechanics in mice in vivo, we developed a miniaturized conductance-manometer system. α-Chloralose-urethan-anesthetized animals were instrumented with a two-electrode pressure-volume catheter advanced via the LV apex to the aortic root. Custom electronics provided time-varying conductances related to cavity volume. Baseline hemodynamics were similar to values in conscious animals: 634 ± 14 beats/min, 112 ± 4 mmHg, 5.3 ± 0.8 mmHg, and 11,777 ± 732 mmHg/s for heart rate, end-systolic and end-diastolic pressures, and maximum first derivative of ventricular pressure with respect to time (dP/d t max), respectively. Catheter stroke volume during preload reduction by inferior vena caval occlusion correlated with that by ultrasound aortic flow probe ( r 2 = 0.98). This maneuver yielded end-systolic elastances of 79 ± 21 mmHg/μl, preload-recruitable stroke work of 82 ± 5.6 mmHg, and slope of dP/d t max-end-diastolic volume relation of 699 ± 100 mmHg ⋅ s−1 ⋅ μl−1, and these relations varied predictably with acute inotropic interventions. The control normalized time-varying elastance curve was similar to human data, further supporting comparable chamber mechanics between species. This novel approach should greatly help assess cardiovascular function in the blood-perfused murine heart.

Regulatory effects of phospholamban on cardiac function in intact mice

1997 ◽  
Vol 273 (6) ◽  
pp. H2826-H2831 ◽  
Author(s):  
John N. Lorenz ◽  
Evangelia G. Kranias
Keyword(s):  
Diastolic Pressure ◽  
Systolic Pressure ◽  
Physiological Role ◽  
Cardiovascular Effects ◽  
Left Ventricular ◽  
In Vivo Evaluation ◽  
Intact Mouse ◽  
Cardiac Sarcoplasmic Reticulum ◽  
Inotropic Effects

Phospholamban (PLB) regulates Ca2+- adenosinetriphosphatase activity in cardiac sarcoplasmic reticulum and participates in the regulation of myocardial performance. Animal models with altered levels of PLB permit in vivo evaluation of the physiological role of PLB. This study examined left ventricular (LV) performance in intact PLB heterozygous and homozygous mice under basal and stimulated conditions. A Millar Mikro-Tip transducer was inserted into the right carotid artery and advanced into the LV for direct measurement of ventricular pressure and the first derivative of intraventricular pressure (dP/d t). Baseline blood pressures were increased in PLB heterozygotes and even more so in PLB homozygotes compared with wild types (WT), and there were no differences in heart rate or LV end-diastolic pressure. The increase in pressure was primarily caused by an increase in systolic pressure. Baseline values for positive and negative dP/d t were linearly correlated with PLB levels. In PLB heterozygotes, contractile response to isoproterenol (Iso) was blunted compared with WT, but maximum rates of contraction were similar between the two groups. Contractile performance in PLB homozygous mice, which under baseline conditions was similar to maximum levels seen in WT, showed a blunted response to Iso, and maximum rates of contraction were significantly greater than in either of the other groups, indicating an essential but perhaps not exclusive role for PLB in mediating the inotropic effects of β-adrenergic agonists. The effects of Iso on negative dP/d t were also blunted in both PLB heterozygous and PLB homozygous animals. Our results demonstrate that myocardial function is highly dependent on PLB level and suggest that the cardiovascular effects of PLB perturbations are largely uncompensated for in the intact mouse.

Relaxation time constant of isolated rabbit left ventricle

1987 ◽  
Vol 253 (3) ◽  
pp. H512-H518
Author(s):  
P. Schiereck ◽  
J. H. Nieuwenhuijs ◽  
E. L. de Beer ◽  
M. W. van Hessen ◽  
F. A. van Kaam ◽  
...  
Keyword(s):  
Time Constant ◽  
Diastolic Pressure ◽  
Time Derivative ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Relaxation Time Constant ◽  
Contraction Phase ◽  
End Diastolic Volume ◽  
The Difference ◽  
First Time

Experiments were performed on isolated rabbit left ventricles. Controlled ejections during otherwise isovolumic contractions were studied. The time constant of relaxation was defined as the slope of the linear approximation of the ln(P)-t relation over a 40-ms period starting 20 ms after the minimum of the first time derivative of left ventricular pressure (dP/dt) of the isovolumic contraction. Variations in time of ejection, its amplitude, and velocity are applied independently. No direct effect of the variations in time and velocity of the ejection on the time constant of relaxation was found. This is in conflict with the findings of Hori et al. (Circ. Res. 55: 31-38, 1984). The difference is due to the influence of the recovery of pressure directly after the end of ejection in their study. This effect is present especially when ejection was timed to take place late in the contraction phase. The effect of the variation of the amplitude of the ejection on the time constant was similar to the effect of the end-diastolic pressure on the end-diastolic volume. It is concluded that the time constant of relaxation depends linearly on the same processes that are responsible for the height of the end-diastolic pressure.

Volume overload hypertrophy in a closed-chest model of mitral regurgitation

1988 ◽  
Vol 254 (6) ◽  
pp. H1034-H1041 ◽  
Author(s):  
J. P. Kleaveland ◽  
W. G. Kussmaul ◽  
T. Vinciguerra ◽  
R. Diters ◽  
B. A. Carabello
Keyword(s):  
Cardiac Output ◽  
Mitral Regurgitation ◽  
Diastolic Pressure ◽  
Volume Ratio ◽  
Volume Overload ◽  
Canine Model ◽  
Left Ventricular ◽  
Closed Chest ◽  
Cardiac Decompensation ◽  
End Diastolic Volume

Chronic volume overload hypertrophy as seen in mitral regurgitation in humans eventually may cause left ventricular dysfunction. Longitudinal study of the mechanisms leading to such dysfunction is difficult in humans and more easily performed in an animal model. In this study, we describe a canine model of volume overload hypertrophy produced by mitral regurgitation. An arterially placed grasping forceps was used to disrupt mitral chordae or leaflets; thus mitral regurgitation was produced without the need for thoracotomy. Eleven of 22 dogs had severe mitral regurgitation (regurgitant fraction greater than 0.50) and survived for greater than or equal to 3 mo (average 9.2 +/- 6 mo) after the production of mitral regurgitation. At 3 mo, end-diastolic volume increased from 48 +/- 9 to 85 +/- 19 ml, P less than 0.01. Left ventricular mass increased from 71 +/- 13 to 90 +/- 10 g, P less than 0.01. Left ventricular end-diastolic pressure increased from 9 +/- 3 to 19 +/- 6 mmHg, P less than 0.01. Cardiac output decreased from 2.3 +/- 0.61 to 1.80 +/- 0.64 l/min, P less than 0.05. The mass-to-volume ratio decreased from 1.44 +/- 0.17 to 1.09 +/- 0.13, P less than 0.01. We conclude that this closed-chest model of chronic mitral regurgitation produces significant eccentric cardiac hypertrophy. Despite a doubling of end-diastolic volume, there was a fall in cardiac output and a rise in left ventricular end-diastolic pressure, suggesting cardiac decompensation.

Effect of lactic acidosis on canine hemodynamics and left ventricular function

1990 ◽  
Vol 258 (4) ◽  
pp. H1193-H1199 ◽  
Author(s):  
K. Teplinsky ◽  
M. O'Toole ◽  
M. Olman ◽  
K. R. Walley ◽  
L. D. Wood
Keyword(s):  
Cardiac Output ◽  
Lactic Acidosis ◽  
Stroke Volume ◽  
Venous Return ◽  
Diastolic Pressure ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
Right Atrial ◽  
Lactic Acidemia

Hypoperfusion states cause lactic acidosis, and the acidemia further reduces the inadequate cardiac output. Conceivably, the adverse effect of lactic acidemia on cardiac output is due to depressed contractility demonstrated in isolated myocardium. Alternatively, factors governing venous return cause a relative hypovolemic state and/or acidemic pulmonary vasoconstriction-induced right ventricular dysfunction. We reasoned that examination of left ventricular pressure-volume relationships at end systole and end diastole would determine which of these potential mechanisms accounted for reduced cardiac output during progressive lactic acidosis in anesthetized, mechanically ventilated dogs. Left ventricular (LV) volume was estimated from two pairs of epicardial ultrasonic crystals placed in the anterior-posterior and longitudinal planes, and LV pressure was obtained rom a catheter-tipped transducer. During progressive acidemia induced by a continuous intravenous infusion of 0.5 N lactic acid, cardiac output, stroke volume, and mean systemic arterial pressure fell significantly while mean pulmonary artery pressure and right atrial pressure increased significantly. These variables did not change with time in control (no-acid infusion) dogs. Lactic acidemia caused a 40% reduction in stroke volume, which could be attributed to depressed LV contractility, characterized by a decrease in maximum dP/dt as well as a fall in slope (Emax) with no change in volume intercept (Vo) of the left ventricular pressure-volume relationship at end systole. Neither the measured left ventricular end-diastolic pressure nor the estimated left ventricular end-diastolic volume (LVEDV) decreased with acidemia, suggesting that the reduced venous return did not result from relative hypovolemia. However, acidemic pulmonary hypertension may have interfered with the expected response to myocardial depression, which is an increase in LVEDV.

Heart size and maximal cardiac output are limited by the pericardium

1992 ◽  
Vol 263 (6) ◽  
pp. H1675-H1681 ◽  
Author(s):  
H. K. Hammond ◽  
F. C. White ◽  
V. Bhargava ◽  
R. Shabetai
Keyword(s):  
Cardiac Output ◽  
Oxygen Consumption ◽  
Diastolic Pressure ◽  
Maximal Oxygen Consumption ◽  
Left Ventricular ◽  
Treadmill Running ◽  
Oxygen Utilization ◽  
End Diastolic Volume ◽  
Maximal Cardiac Output ◽  
Heart Size

We tested the hypothesis that the pericardium, by restricting heart size, limits maximal cardiac output and oxygen consumption. We studied 15 pigs. Five underwent maximal treadmill running before and 14–21 days after thoracotomy and pericardiectomy; these pigs also received sequential volume infusions to determine end-diastolic pressure-dimension relationships. Five underwent maximal treadmill running before and 14–21 days after thoracotomy (pericardium undisturbed) to determine the effect of thoracotomy on exercise performance. Finally, five underwent thoracotomy, instrumentation, loose closure of the pericardium, and sequential volume infusions to determine the effect of thoracotomy without pericardiectomy on end-diastolic pressure-dimension relationships. Pericardiectomy caused similar increases in maximal cardiac output (29% increase; P = 0.007) and maximal oxygen consumption (31% increase; P = 0.02). These results were associated with increased left ventricular end-diastolic dimension (10% increase; P = 0.01) and an estimated 33% increase in end-diastolic volume. In addition, left ventricular mass was increased by pericardiectomy (18% increase; P < 0.04). Thus the pericardium, by limiting utilization of the Starling mechanism, limits maximal cardiac output, and the limit to cardiorespiratory performance lies not in oxygen utilization, but in oxygen delivery. Furthermore, removal of pericardium is associated with myocardial hypertrophy.

cGMP-independent inotropic effects of nitric oxide and peroxynitrite donors: potential role for nitrosylation

2000 ◽  
Vol 279 (4) ◽  
pp. H1982-H1988 ◽  
Author(s):  
Nazareno Paolocci ◽  
Ulf E. G. Ekelund ◽  
Takayoshi Isoda ◽  
Michitaka Ozaki ◽  
Koenraad Vandegaer ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Guanylyl Cyclase ◽  
Pressure Rise ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
No Donor ◽  
Inotropic Effects ◽  
Iron Nitrosyl ◽  
Rat Hearts

Nitric oxide (NO) has concentration-dependent biphasic myocardial contractile effects. We tested the hypothesis, in isolated rat hearts, that NO cardiostimulation is primarily non-cGMP dependent. Infusion of 3-morpholinosydnonimine (SIN-1, 10−5 M), which may participate in S-nitrosylation (S-NO) via peroxynitrite formation, increased the rate of left ventricular pressure rise (+dP/d t; 19 ± 4%, P < 0.001, n = 11) without increasing effluent cGMP or cAMP. Superoxide dismutase (SOD; 150 U/ml) blocked SIN-1 cardiostimulation and led to cGMP elaboration. Sodium nitroprusside (10−10–10−7 M), an iron nitrosyl compound, did not augment +dP/d t but increased cGMP approximately eightfold ( P < 0.001), whereas diethylamine/NO (DEA/NO; 10−7 M), a spontaneous NO· donor, increased +dP/d t (5 ± 2%, P < 0.05, n = 6) without augmenting cGMP. SIN-1 and DEA/NO +dP/d t increase persisted despite guanylyl cyclase inhibition with 1 H-(1,2,4)oxadiazolo-(4,3,- a)quinoxalin-1-one (10−5 M, P < 0.05 for both donors), suggesting a cGMP-independent mechanism. Glutathione (5 × 10−4 M, n = 15) prevented SIN-1 cardiostimulation, suggesting S-NO formation. SIN-1 also produced SOD-inhibitable cardiostimulation in vivo in mice. Thus peroxynitrite and NO donors can stimulate myocardial contractility independently of guanylyl cyclase activation, suggesting a role for S-NO reactions in NO/peroxynitrite-positive inotropic effects in intact hearts.

scholarly journals Left ventricular pressure-volume relationship in a rat model of advanced aging-associated heart failure

2004 ◽  
Vol 287 (5) ◽  
pp. H2132-H2137 ◽  
Author(s):  
Pál Pacher ◽  
Jon G. Mabley ◽  
Lucas Liaudet ◽  
Oleg V. Evgenov ◽  
Anita Marton ◽  
...  
Keyword(s):  
Diastolic Pressure ◽  
Systolic Pressure ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Male Rats ◽  
Ventricular Pressure ◽  
Stroke Work ◽  
Effective Prevention ◽  
Fischer 344 ◽  
End Diastolic Volume

Aging is associated with profound changes in the structure and function of the heart. A fundamental understanding of these processes, using relevant animal models, is required for effective prevention and treatment of cardiovascular disease in the elderly. Here, we studied cardiac performance in 4- to 5-mo-old (young) and 24- to 26-mo-old (old) Fischer 344 male rats using the Millar pressure-volume (P-V) conductance catheter system. We evaluated systolic and diastolic function in vivo at different preloads, including preload recruitable stroke work (PRSW), maximal slope of the systolic pressure increment (+dP/d t), and its relation to end-diastolic volume (+dP/d t-EDV) as well as the time constant of left ventricular pressure decay, as an index of relaxation. The slope of the end-diastolic P-V relation (EDPVR), an index of left ventricular stiffness, was also calculated. Aging was associated with decrease in left ventricular systolic pressure, +dP/d t, maximal slope of the diastolic pressure decrement, +dP/d t-EDV, PRSW, ejection fraction, stroke volume, cardiac and stroke work indexes, and efficiency. In contrast, total peripheral resistance, left ventricular end-diastolic volume, left ventricular end-diastolic pressure, and EDPVR were greater in aging than in young animals. Taken together, these data suggest that advanced aging is characterized by decreased systolic performance accompanied by delayed relaxation and increased diastolic stiffness of the heart in male Fischer 344 rats. P-V analysis is a sensitive method to determine cardiac function in rats.

Ketamine, but Not S  (+)-ketamine, Blocks Ischemic Preconditioning in Rabbit Hearts In Vivo 

2001 ◽  
Vol 94 (4) ◽  
pp. 630-636 ◽  
Author(s):  
Jost Müllenheim ◽  
Jan Fräßdorf ◽  
Benedikt Preckel ◽  
Volker Thämer ◽  
Wolfgang Schlack
Keyword(s):  
Cardiac Output ◽  
Coronary Artery ◽  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Left Ventricular Pressure ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Left Ventricular ◽  
Ventricular Pressure

Background Ketamine blocks KATP channels in isolated cells and abolishes the cardioprotective effect of ischemic preconditioning in vitro. The authors investigated the effects of ketamine and S(+)-ketamine on ischemic preconditioning in the rabbit heart in vivo. Methods In 46 alpha-chloralose-anesthetized rabbits, left ventricular pressure (tip manometer), cardiac output (ultrasonic flow probe), and myocardial infarct size (triphenyltetrazolium staining) at the end of the experiment were measured. All rabbits were subjected to 30 min of occlusion of a major coronary artery and 2 h of subsequent reperfusion. The control group underwent the ischemia-reperfusion program without preconditioning. Ischemic preconditioning was elicited by 5-min coronary artery occlusion followed by 10 min of reperfusion before the 30 min period of myocardial ischemia (preconditioning group). To test whether ketamine or S(+)-ketamine blocks the preconditioning-induced cardioprotection, each (10 mg kg(-1)) was administered 5 min before the preconditioning ischemia. To test any effect of ketamine itself, ketamine was also administered without preconditioning at the corresponding time point. Results Hemodynamic baseline values were not significantly different between groups [left ventricular pressure, 107 +/- 13 mmHg (mean +/- SD); cardiac output, 183 +/- 28 ml/min]. During coronary artery occlusion, left ventricular pressure was reduced to 83 +/- 14% of baseline and cardiac output to 84 +/- 19%. After 2 h of reperfusion, functional recovery was not significantly different among groups (left ventricular pressure, 77 +/- 19%; cardiac output, 86 +/- 18%). Infarct size was reduced from 45 +/- 16% of the area at risk in controls to 24 +/- 17% in the preconditioning group (P = 0.03). The administration of ketamine had no effect on infarct size in animals without preconditioning (48 +/- 18%), but abolished the cardioprotective effects of ischemic preconditioning (45 +/- 19%, P = 0.03). S(+)-ketamine did not affect ischemic preconditioning (25 +/- 11%, P = 1.0). Conclusions Ketamine, but not S(+)-ketamine blocks the cardioprotective effect of ischemic preconditioning in vivo.

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