Special Communication

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. alpha-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/dtmax), respectively. Catheter stroke volume during preload reduction by inferior vena caval occlusion correlated with that by ultrasound aortic flow probe (r2 = 0.98). This maneuver yielded end-systolic elastances of 79 +/- 21 mmHg/microliter, preload-recruitable stroke work of 82 +/- 5.6 mmHg, and slope of dP/dtmax-end-diastolic volume relation of 699 +/- 100 mmHg.s-1.microliter-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.

[1]  W. Hamilton,et al.  BLOOD PRESSURE STUDIES IN SMALL ANIMALS , 1937 .

[2]  K. Chien Molecular advances in cardiovascular biology. , 1993, Science.

[3]  M. Pinsky,et al.  Dynamic right and left ventricular interactions in the rabbit: simultaneous measurement of ventricular pressure-volume loops. , 1996, Journal of critical care.

[4]  R. Hammond,et al.  Chronic Changes of End‐Systolic Pressure‐Volume Relationship After Regional Myocardial Infarction , 1995, Journal of cardiac surgery.

[5]  N Westerhof,et al.  Normalized input impedance and arterial decay time over heart period are independent of animal size. , 1991, The American journal of physiology.

[6]  Frederick J. Schoen,et al.  A Mouse Model of Familial Hypertrophic Cardiomyopathy , 1996, Science.

[7]  J. P. Holt,et al.  Ventricular volumes and body weight in mammals. , 1968, The American journal of physiology.

[8]  R. Lefkowitz,et al.  Enhanced Myocardial Function inTransgenic Mice Overexpressing theP2-Adrenergic Receptor , 1994 .

[9]  E. T. van der Velde,et al.  Continuous stroke volume and cardiac output from intra-ventricular dimensions obtained with impedance catheter. , 1981, Cardiovascular research.

[10]  D. Kass,et al.  Diminished Contractile Response to Increased Heart Rate in Intact Human Left Ventricular Hypertrophy Systolic Versus Diastolic Determinants , 1993, Circulation.

[11]  J. Sapirstein,et al.  Left ventricular mechanoenergetics during asynchronous left atrial-to-aortic bypass. Effects of pumping rate on cardiac workload and myocardial oxygen consumption. , 1995, The Journal of thoracic and cardiovascular surgery.

[12]  S Sasayama,et al.  Ventriculoarterial coupling in normal and failing heart in humans. , 1989, Circulation research.

[13]  W. Little,et al.  The Left Ventricular dP/dtmax‐End‐Diastolic Volume Relation in Closed‐Chest Dogs , 1985, Circulation research.

[14]  L A Geddes,et al.  Continuous measurement of ventricular stroke volume by electrical impedance. , 1966, Cardiovascular Research Center bulletin.

[15]  J. A. Micales,et al.  PHYSIOLOGICAL CHARACTERISTICS OF A , 1989 .

[16]  B Buis,et al.  Continuous measurement of left ventricular volume in animals and humans by conductance catheter. , 1984, Circulation.

[17]  H. Suga,et al.  Left ventricular volumetric conductance catheter for rats. , 1996, The American journal of physiology.

[18]  David A. Kass,et al.  Effective Arterial Elastance as Index of Arterial Vascular Load in Humans , 1992, Circulation.

[19]  T. Kishimoto,et al.  Continuous activation of gp130, a signal-transducing receptor component for interleukin 6-related cytokines, causes myocardial hypertrophy in mice. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[20]  G. Olinger,et al.  Standardization of end-systolic pressure-volume relation in the dog. , 1985, The American journal of physiology.

[21]  C. H. Chen,et al.  Single-beat estimation of end-systolic pressure-volume relation in humans. A new method with the potential for noninvasive application. , 1996, Circulation.

[22]  G Grupp,et al.  Comparison of normal, hypodynamic, and hyperdynamic mouse hearts using isolated work-performing heart preparations. , 1993, The American journal of physiology.

[23]  佐川 喜一,et al.  Cardiac contraction and the pressure-volume relationship , 1988 .

[24]  D. Glower,et al.  Linearity of the Frank-Starling relationship in the intact heart: the concept of preload recruitable stroke work. , 1985, Circulation.

[25]  T. Doetschman,et al.  Targeted ablation of the phospholamban gene is associated with markedly enhanced myocardial contractility and loss of beta-agonist stimulation. , 1994, Circulation research.

[26]  P. Steendijk,et al.  Left ventricular stroke volume by single and dual excitation of conductance catheter in dogs. , 1993, The American journal of physiology.

[27]  Rodney W. Salo,et al.  Measurement of Ventricular Volume by Intracardiac Impedance: Theoretical and Empinrcal Approaches , 1986, IEEE Transactions on Biomedical Engineering.