Right ventricle-sparing heart transplantation effective against iatrogenic pulmonary hypertension.

Abstract

BACKGROUND:

Right heart failure is the predominant cause of death following heart transplantation, occurring with disturbingly high frequency in patients with severe antecedent pulmonary hypertension. We have recently reported a novel technique of heart transplantation that spares the recipient right ventricle, excising only the recipient left ventricle. The resulting model has 2 right hearts and 1 left heart. The aim is to preserve the recipient's right ventricle, which is already conditioned to pulmonary hypertension. The hope is that, in this way, death due to right heart failure can be prevented in humans. Our prior report was a feasibility study in normal dogs. This study challenges this new technique by creating iatrogenic pulmonary hypertension in the recipient animals.

METHODS:

Iatrogenic pulmonary hypertension was created in 4 recipient canines by intravenous injection of the pulmonary toxin monocrotaline pyrrole (single bolus of 3.5 to 4.5 mg/kg intravenously [i.v.]).

RESULTS:

Within 6 weeks of monocrotaline administration, relative pulmonary hypertension occurred (mean pulmonary artery [PA] pressure 20 mm Hg vs 10 mm Hg for controls [p < 0.01]) (pulmonary vascular resistance [PVR] 4.2 vs 1.5 Wood units [P < 0.01]), and right ventricular (RV) hypertrophy developed (RV thickness 11 mm vs 2 mm [P < 0.04]). Histologic examination confirmed severe muscle infiltration and thickening of the media of the pulmonary arterioles. RV-sparing heart transplantation was performed successfully in all 4 animals with pulmonary hypertension. In all cases, the animals were weaned without difficulty from cardiopulmonary bypass, despite the ambient pulmonary hypertension, on low-dose epinephrine, maintaining systolic blood pressure of 104 mm Hg at right atrial pressure of 7 mm Hg. Both right hearts contracted well without dilation or strain. A single "control" traditional orthotopic transplant experiment in an animal with monocrotaline-induced pulmonary hypertension resulted in immediate death from right heart failure.

CONCLUSIONS:

Right ventricle-sparing heart transplantation ("one-and-one-half heart model") can handle pulmonary hypertension without difficulty. This evidence adds impetus for further pursuing of right ventricle-sparing heart transplantation to decrease the incidence of death from right heart failure in recipients with severe antecedent pulmonary hypertension.

• Authors: Constantinos Lovoulos, Shawn Tittle, Lee Goldstein, David J Austin, Simran Singh, Edward Rocco, James Keane, Ping Tang, Gary S Kopf, John A Elefteriades
• Journal: The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation (J Heart Lung Transplant) Vol. 23 Issue 2 Pg. 236-41 (Feb 2004) ISSN: 1053-2498 [Print] United States
• PMID: 14761772 (Publication Type: Journal Article)

Chemical References

• Alkylating Agents
• monocrotaline pyrrole
• Monocrotaline

Topics

• Alkylating Agents
• Animals
• Dogs
• Heart Transplantation (methods)
• Heart Ventricles
• Hypertension, Pulmonary (chemically induced, physiopathology)
• Hypertrophy, Right Ventricular (etiology, physiopathology)
• Iatrogenic Disease
• Monocrotaline (analogs & derivatives)