Barry J. Byrne

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

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.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.

Pulse pressure-related changes in coronary flow in vivo are modulated by nitric oxide and adenosine.

Acute increases in arterial pulsatile load imposed on the left ventricle can increase coronary flow without commensurate changes in myocardial oxygen consumption. One explanation is that augmenting pulsatile perfusion at the same mean pressure itself stimulates flow by releasing endothelium-mediated vasorelaxant factors such as NO. The present study tested this hypothesis and determined whether NO and adenosine modulate this response. In open-chest anesthetized dogs, the distal left anterior descending coronary artery (LAD) was whole-blood-perfused by a novel servopump system to control mean and pulsatile perfusion pressure within the isolated vascular bed. Central aortic pressure was measured, stored to computer memory, and then digitally modified (varying the pulse pressure [PP]) to generate a real-time servocommand that was still synchronous with ventricular contraction. Left heart workload was unchanged. LAD flow was measured before and after increasing the PP (to 60 to 100 mm Hg) from baselines of either 0 or 40 mm Hg. With normal basal coronary vascular tone, raising the PP increased flow (+9 +/- 2% at a PP of 100 mm Hg). This response was markedly amplified (+39 +/- 8%) when basal tone was first partially reduced by adenosine. Competitive inhibition of NO synthase by N omega-monomethyl-L-arginine reduced acetylcholine and PP-dependent flow responses by 50%. Thus, enhanced pulsatile perfusion increases in vivo coronary flow in part by triggering NO release. The marked augmentation of the PP response with reduced basal coronary tone from adenosine suggests that this mechanism may play a role in improving myocardial perfusion during exercise.

A simple new model of physiologically working heterotopic rat heart transplantation provides hemodynamic performance equivalent to that of an orthotopic heart

BACKGROUNDnThe widely used non-volume-loaded abdominal heterotopic heart transplant (NL) in rats undergoes atrophy after transplantation. Various techniques have been designed to load the transplanted heart because of its potential immunological impact. Our aim was to create a volume-loaded heterotopic heart transplantation model (VL) capable of ejection and practical for routine studies. Using this model, we tested the hypothesis that VL isografts would retain myocardial performance comparable to native hearts (NH).nnnMETHODSnHeterotopic hearts were transplanted using and end-to-side anastomosis between the donors superior vena cava and the recipients abdominal inferior vena cava. The right ventricle loads the left ventricle (LV) via a direct anastomosis of the pulmonary artery to the left atrium. The LV ejects volume through an end-to-side anastomosis of the donors aorta to the recipients abdominal aorta. Hemodynamic data (systolic and diastolic LV pressures, dP/dt max and min, tau) were studied in-situ (at baseline and after adding volume) and in a Langendorff perfusion system (at baseline and after stimulation with isoproterenol) 2 weeks after transplantation.nnnRESULTSnIn situ systolic pressure and diastolic function of VL was superior to NL, and beta-adrenergic stimulated performance in the Langendorff perfusion of VL showed hemodynamic performance equivalent to NH, unlike NL which had a diminished response.nnnCONCLUSIONnThis technique results in a volume-loaded ejecting heart transplant model that preserves anatomical structures. The VL can be evaluated in situ and after explantation in Langendorff perfusion system and may offer advantages if workload of the graft is of significance to the study performed.

Abdominal Pain as a Presenting Symptom of Supraventricular Tachycardia

bdominal pain is a com/ ~ mon complaint in young A children, with an extensive differential diagnosis.’ The onset, acuity or chronicity of the pain; its character; and associated symptoms may help narrow the differential diagnosis. However, in many cases the etiology of abdominal pain remains elusive in spite of the most complete evaluation and best diagnostic methodology. When the cause of abdominal