Technique Article

Technique of Complete Heart Isolation with Continuous Cardiac Perfusion During Cardiopulmonary Bypass: New Opportunities for Gene Therapy

^* Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, New York
^† Abington Memorial Hospital, Abington, Pennsylvania
^‡ Sanger Heart and Vascular Institute, Charlotte, North Carolina; and
^§ Main Line Hospital Lankenau, Wynnewood, Pennsylvania

Address correspondence to: Michael G. Katz, MD, PhD, Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, P.O. Box 1030, New York, NY 10029-6574. E-mail: michael.katz1@mssm.edu

Received: 1 November 2017
Accepted: 28 April 2018

Abstract

Cardiopulmonary bypass (CPB) featuring complete heart isolation and continuous cardiac perfusion is a very promising approach for solving the problem of efficient gene delivery. In the technique presented here, separate pumps are used for the systemic and cardiac circuits. This system permits continuous isolated arrested heart perfusion through optimizing a number of delivery parameters including temperature, flow rate, driving pressure, ionic composition, and exposure time to the cardiac vessels. During complete cardiac isolation, the blood vector concentration trended from 11.51 ± 1.73 log genome copies (GCs)/cm³ to 9.84 ± 1.65 log GC/cm³ (p > .05). Despite restructuring a very high concentration to the heart, GCs were detectable in the systemic circuit. These values over time were near negligible by comparison but detectable 1.66 ± .26 during 20 minutes of recirculation and did not change (p > .05). After the completion of the recirculation interval and subsequent washing procedure, the initial systemic blood vector GC concentration slightly increased to 2.08 ± .38 log GCs/cm³ (p > .05). During the recirculation period, we supported flow via the cardiac circuit around 300 mL/min. In this technique of heart isolation with continuous cardiac perfusion, >99% of the vector remains in coronary circulation during recirculation period. The animal’s non recirculation blood, or that in the system, was routinely tested during and after recirculation to contain much less than 1% of the original dose obtained via logging concentration of therapeutic over time. All of the sheep in this group recovered from anesthesia and received critical postoperative care, including all organ function, in the first 24–36 hours. Twenty-one sheep (84%) survived to euthanasia at 12 weeks. Average CPB time was 107 ± 19.0 minutes and cross-clamp time was 49 ± 7.9 minutes. This technology readily provides multiple pass recirculation of genes through the heart with minimal side effects of collateral expression of other organs.