Is profound hypothermia required for storage of cardiac allografts?

BACKGROUND: Improved methods of cardiac allograft protection are required to expand the pool of potentially available organs and to enhance the recovery of grafts subjected to prolonged ischemia. We have previously demonstrated that limited coronary perfusion provided by donor blood harvested at the time of organ procurement can improve both metabolic and functional recovery after transplantation. In this study we evaluated the hypothesis that limited coronary perfusion may enable prolonged cardiac storage while avoiding the potentially detrimental effects of profound hypothermia. METHODS: Fourteen orthotopic cardiac transplants were performed in female Yorkshire pigs by using donor blood perfusion during 5 hours of either tepid (25 degrees C) or cold (4 degrees C) storage. Assessments of myocardial metabolism and function were performed at baseline and after 45 minutes of normothermic (37 degrees C) reperfusion. RESULTS: Hearts protected with tepid perfusion displayed improved recovery of myocardial function (89% +/- 18% vs 63% +/- 25%, P =.05). Diastolic compliance was adversely affected in both groups after transplantation. Aerobic myocardial metabolism was better preserved in the tepid group. CONCLUSIONS: Profound hypothermia results in depressed myocardial metabolic and functional recovery after transplantation. Limited coronary perfusion with shed donor blood can permit cardiac allograft storage at tepid temperatures, resulting in improved myocardial performance.

Acute graded hypercapnia increases collateral coronary blood flow in a swine model of chronic coronary artery obstruction.

OBJECTIVE: To evaluate the effect of acute hypercapnia on regional myocardial blood flow in a swine model of chronic, single-vessel coronary artery obstruction. Permissive hypercapnia is being used frequently in critical care settings. One possible detrimental effect of hypercapnia is the initiation of coronary "steal" in patients with coronary artery disease. The effects of hypercapnia on collateral coronary blood flow in the setting of coronary obstruction have not been defined. DESIGN: Prospective controlled experimental study. SETTING: Institutional animal research facility. SUBJECTS: Eight juvenile swine weighing 25-30 kg. INTERVENTIONS: Collateral coronary circulation was induced in eight piglets by banding the proximal left anterior descending coronary artery for 8-10 wks followed by total ligation. Graded hypercapnia (mean Paco2, 81 torr [10.80 kPa; Paco2 = 81 torr] and 127 torr [16.93 kPa; Paco2 = 127 torr]) was induced by increasing inspiratory carbon dioxide under isoflurane anesthesia (1 minimum alveolar concentration). MEASUREMENTS AND MAIN RESULTS: Animals were attached to instruments to measure pulmonary and systemic hemodynamics, regional myocardial blood flow, and cardiac output. Regional myocardial blood flow was determined using radiolabeled microspheres. Cardiac output, mean arterial pressure, and coronary perfusion pressure were unchanged at both levels of hypercapnia compared with baseline values. Heart rate was increased at Paco2 [HI] (p < .05). Regional blood flow was increased at both levels of hypercapnia in the collateral-dependent and normally perfused myocardium (p < .05; as high as 56% for subendocardium and as high as 106% for subepicardium at Paco2 [HI]). The intercoronary blood flow ratio remained unaltered. The transmural flow ratio was reduced at Paco2 [HI] (P < .05). During hypercapnia, regional lactate extraction remained unaltered, and regional oxygen extraction was unchanged or reduced despite the increase in oxygen consumption. CONCLUSIONS: In this swine model of chronic single-vessel coronary artery obstruction, acute hypercapnia does not induce coronary steal from collateral-dependent myocardium, but it does increase global coronary blood flow.

Donor blood perfusion improves myocardial recovery after heart transplantation.

BACKGROUND: Improved methods of donor heart preservation may allow for prolonged storage and permit remote procurement. Previous attempts to use oxygenated perfusion circuits during storage have not gained widespread acceptance because they were either too impractical or complicated to use for remote harvest. We hypothesized that collection and perfusion of donor blood during prolonged storage may improve myocardial recovery. Our aim was to devise a safe, simple, cost-effective system that could be used in any hospital setting. METHODS: Yorkshire pigs (40 to 50 kg) were used to perform 16 orthotopic heart transplantations with either continuous perfusion with donor blood (BL, n = 8) or standard hypothermic storage (CON, n = 8). After administration of heparin, hypothermic (4 degrees C) cardioplegic arrest, and donor heart extraction, donor blood (2688 +/- 166 ml) was harvested in the BL group. After filtration for particulate matter, blood perfusion was initiated via a standard intravenous transfusion apparatus at room temperature (20 degrees C) and a pressure of 60 mm Hg and maintained during storage. Arterial and coronary sinus blood samples were obtained to examine myocardial oxygen extraction, lactate release, and acid production. A Millar micromanometer was used to measure left ventricular developed pressures at an end-diastolic pressure of 2 and 10 mm Hg both before and after transplantation. RESULTS: All pigs (eight of eight) in the BL group were successfully weaned off bypass compared to three of eight in the CON group (p < 0.01). Developed pressures (at left ventricular end-diastolic pressure = 10 mm Hg) was improved in the BL group (mean +/- SD: baseline: BL: 90 +/- 16 mm Hg vs CON: 83 +/- 12 mm Hg, p = NS; posttransplantation: BL: 66 +/- 8 mm Hg vs CON: 35 +/- 29 mm Hg, p < 0.05). Similarly, maximum dP/dt was higher in the BL group. Lactate release was higher at cross-clamp removal in the BL group (2.4 +/- 0.3 mmol/L vs 0.7 +/- 0.2 mmol/L, p < 0.01). There were no differences in oxygen extraction or acid production during reperfusion. CONCLUSIONS: Perfusion of donor blood improved the ability to wean off bypass after 4 hours of storage. Blood perfusion permitted persistent myocardial metabolism during the ischemic period, which led to improved functional recovery. Harvesting donor blood for subsequent perfusion during prolonged storage may improve the results of orthotopic heart transplantation and allow for more distant procurement of donor organs.

Cocaine toxicity and isoflurane anesthesia: hemodynamic, myocardial metabolic, and regional blood flow effects in swine.

OBJECTIVES: Increasing numbers of people use cocaine recreationally and may require anesthesia care, having recently abused the drug. However, no data currently exist concerning potential interactions between toxic levels of cocaine and volatile anesthetic agents. This study investigated the effects of cocaine infusion on systemic hemodynamics, myocardial metabolism, and regional organ blood flow in relation to depth of isoflurane anesthesia. DESIGN: Prospective, randomized, controlled trial. SETTING: A laboratory at a university medical center. PARTICIPANTS: Twelve miniature pigs. INTERVENTIONS: An open-chest swine model was used. Isoflurane (ISO) was the sole anesthetic, administered at 0.75 and 1.5 minimum alveolar concentration (MAC), and cocaine was infused (n = 6) at a rate of 0.5 mg/kg/min. Control animals (n = 6) received an equivalent amount of normal saline. MEASUREMENTS AND MAIN RESULTS: Systemic and pulmonary arterial pressures and thermodilution cardiac output data were collected at 0.75 MAC and 1.5 MAC ISC. Regional myocardial and blood flows to other organs were measured using radiolabeled microspheres. Arrhythmias and altered ventricular conduction were noted only in the cocaine group, along with significant elevations in diastolic arterial pressure, coronary perfusion pressure, and systemic vascular resistance. Increased subendocardial blood flow occurred during cocaine infusion (p = 0.03); subepicardial perfusion was unchanged. Cerebral (p < 0.01) and spinal cord (p < 0.05) blood flows were reduced in animals receiving cocaine. Other organ blood flows were unchanged with depth of anesthesia or cocaine administration, with the exception of splenic blood flow (p < 0.04). CONCLUSIONS: Moderately toxic cocaine levels occurring during isoflurane at 0.75 MAC and 1.5 MAC are associated with hemodynamic abnormalities, a marked increase in systemic vascular resistance, and a tendency to produce cardiac arrhythmias. A reversal of endo/epicardial myocardial perfusion ratio occurs associated with cocaine infusion during ISO anesthesia. This is probably not related to a primary redistribution of subendocardial blood flow and may be related to a combination of increased myocardial oxygen demand and epicardial coronary vasoconstriction. The reductions in cerebral and spinal cord perfusion observed may explain, in part, the neurologic sequelae of cocaine toxicity.

Comparison of nifedipine and metoprolol on collateral coronary blood flow in a swine model of chronic coronary obstruction and acute ischaemia during isoflurane anaesthesia.

PURPOSE: This study compared the effects of nifedipine and metoprolol on collateral-dependent myocardial blood flow in a swine model of chronic coronary obstruction and acute ischaemia during isoflurane anaesthesia. METHODS: Collateral coronary circulation was induced in 15 three-week-old piglets by banding of the proximal left anterior descending coronary artery (LAD). After 8-10 wk, the distal LAD was ligated and the open-chest pigs were randomized to receive infusions of either saline, nifedipine (5 micrograms.kg-1.min-1) or metoprolol (10 micrograms.kg-1.min-1) for 30 min during isoflurane anaesthesia (2%). Transient ischaemia was induced by 30 sec occlusion of the left circumflex artery. Arterial blood pressures, heart rate and regional myocardial blood flow (radiolabelled microspheres technique) were measured at the end of drug infusion (baseline) and one minute after transient ischaemia. RESULTS: No differences in the blood flow to the collateral-dependent (CD) myocardium or haemodynamic variables were observed at baseline among the three groups. Following transient ischaemia, in the nifedipine but not in the metoprolol group, blood flow to the CD myocardium was reduced by 28 +/- 24% in the epicardium (P < 0.05) and 56 +/- 20% in the endocardium (P < 0.01), resulting from intercoronary and transmural steal. This was associated with a moderate increase (10%, P < 0.05) in the heart rate in the nifedipine group. CONCLUSIONS: In a swine model of chronic coronary obstruction and acute ischaemia during isoflurane anaesthesia, the collateral coronary blood flow was maintained in the presence of metoprolol, but reduced in the presence of nifedipine following transient ischaemia due to intercoronary and transmural steal.

Salvage of ischemic myocardium by nonsynchronized retroperfusion in the pig.

Salvage of ischemic myocardium, with the aid of a nonsynchronized coronary sinus retroperfusion system, was studied in a pig infarct model. In anesthetized open chested animals, the left anterior descending coronary artery was occluded for 4 hours and then reperfused for 1 hour before the animals were killed. In the control group (n = 12) no therapy was used. In the experimental group (n = 13), nonsynchronized retrovenous coronary sinus perfusion was applied during the 4 hours of coronary artery occlusion. Therapy consisted of intermittent balloon occlusion of the coronary sinus (5-second inflation, 5-second deflation) with retroperfusion of arterial blood at 60 ml/min during the inflation part of the cycle. Infarct size, expressed as a percentage of the area at risk (+/- standard deviation), was significantly smaller in the experimental group (41.5% +/- 15.0%) than in the control group (80.5% +/- 6.1%) (p less than 0.001). Mean coronary sinus pressure (+/- standard deviation) was 51 +/- 12 mm Hg in the experimental group but was not elevated in the control animals. We conclude that nonsynchronized retrovenous coronary sinus perfusion was able to significantly salvage ischemic myocardium in a model of minimal intercoronary collateral circulation.