Paul A. Chang

Gross and microvascular distribution of retrograde cardioplegia in explanted human hearts

In this report, explanted hearts from transplant recipients with the diagnosis of idiopathic cardiomyopathy underwent a blood cardioplegia arrest and extended subatrial resection to preserve their coronary sinus venous system. The coronary sinus and left and right coronary arteries were then cannulated and warm blood cardioplegia retrograde infused at a pressure of 30 to 40 mm Hg. Effluent from the coronary arteries and thebesian veins was then collected. Hearts were subsequently fixed with retrograde glutaraldehyde perfusion and perfused retrograde with NTB-2 (an inert intracapillary marker). Histologic sections were examined from 12 separate sites. There was no significant difference in the percentage of capillaries perfused by retrograde-delivered cardioplegia between corresponding regions of the left and right ventricles. However, effluent analysis indicated that 67.2% +/- 6.4% of retrograde-delivered blood cardioplegia was shunted through thebesian veins, thereby bypassing the microvasculature, whereas 29.3% +/- 6.3% and 3.5% +/- 3.1% traversed the myocardium supplied by the left and right coronary arteries, respectively. The results indicate that all regions of both ventricles are perfused by retrograde blood cardioplegia. However, they also suggest that nutrient flow to the microvasculature of the right ventricle is minimal during retrograde cardioplegia.

l-Arginine Administration During Reperfusion Improves Pulmonary Function

BACKGROUND Nitric oxide is crucial to the maintenance of vascular homeostasis. Because nitric oxide levels decline upon lung reperfusion, infusion of L-arginine, a nitric oxide precursor, during reperfusion might prove effective at ameliorating reperfusion injury. METHODS Neonatal piglet heart-lung blocks were preserved with Euro-Collins solution for 12 hours, rewarmed at room temperature for 1 hour, and reperfused for 10 minutes with either whole blood (n = 5), whole blood containing L-arginine (10 mmol/L; n = 6), or leukocyte-depleted blood (n = 6) on an isolated, blood-perfused, working heart-lung circuit. After the initial 10 minutes, all blocks received whole blood for 4 hours. Control blocks were continuously perfused on the circuit without intervening ischemia (n = 6). RESULTS The partial pressure of oxygen in the whole blood group (113.8 +/- 33.1 mm Hg) was significantly less than in controls (417.3 +/- 6.2 mm Hg; p < 0.01). Lung compliance was significantly less in the whole blood group (0.8 +/- 0.2 mL/cm H2O) than in controls (2.9 +/- 0.4 mL/cm H2O; p < 0.01). The L-arginine and leukocyte-depleted blood groups showed no significant difference from controls. CONCLUSIONS L-Arginine infusion during reperfusion improves pulmonary function, making it a simple alternative to leukocyte depletion.

Evidence of improved microvascular perfusion when using antegrade and retrograde cardioplegia

BACKGROUND The maximum degree of microvascular distribution of cardioplegic solution is considered important to achieve optimum myocardial protection. This study attempts to demonstrate that the addition of retrograde cardioplegia to antegrade cardioplegia improves overall microvascular perfusion. METHODS Explanted human hearts (n = 6) were treated with cold cardioplegic arrest and bicaval cardiectomy. Blood cardioplegia (37 degrees C) containing colored microspheres (color A for antegrade, color B for retrograde) was simultaneously infused antegrade at a pressure of 80 mm Hg and retrograde at a pressure of 40 mm Hg for 2 minutes. The ventricular myocardium was then sampled at three sites to determine absolute and relative cardioplegic microvascular flow. RESULTS Of the total microvascular capillary flow, 27% to 32% was found to be the contribution of retrogradely delivered cardioplegia. CONCLUSIONS Despite being delivered simultaneously and at a lower pressure, retrograde cardioplegia contributed substantially to overall microvascular perfusion. This suggests that antegrade cardioplegia alone does not perfuse all available myocardial capillaries and that the addition of retrograde cardioplegia enhances overall microvascular distribution and perfusion.

Can improved microvascular perfusion be achieved by using both antegrade and retrograde cardioplegia

BACKGROUND The complete and uniform distribution of cardioplegia to the microvasculature of the heart is considered critical for myocardial protection. This study explores the hypothesis that enhanced microvascular perfusion can be achieved by using both antegrade and retrograde cardioplegia. METHODS Infant piglet hearts (n = 15) were arrested with antegrade blood cardioplegia, excised, and fixed with 2.5% glutaraldehyde by retrograde perfusion. Hearts were then perfused retrograde with an inert intracapillary marker (NTB-2). Six of these hearts served as controls (group 1) to anatomically demonstrate the degree of capillary perfusion achieved by the retrograde delivery route. Nine experimental hearts (group 2) underwent a subsequent infusion of antegrade blood cardioplegia to wash out NTB-2 capillaries coperfused by both the antegrade and retrograde delivery techniques. Sections of the left ventricular free wall and anterior-mid interventricular septum were taken and examined by light microscopy at four separate sites (average, 126 capillaries per section). RESULTS In control hearts, 91.9% +/- 0.9% of ventricular capillaries and 91.4% +/- 5.8% of septal capillaries were perfused by retrograde cardioplegia. After antegrade blood cardioplegia washed out group 2 hearts, 14.0% +/- 4.1% of capillaries in the ventricle still contained NTB-2, as did 12.5% +/- 5.4% of capillaries in the septum. CONCLUSIONS In this experimental model, antegrade blood cardioplegia did not coperfuse (and therefore washout) 12.5% to 14% (p < 0.05) of capillaries perfused by retrograde cardioplegia. This suggests that an additional 12.5% to 14% of capillaries within the myocardium may receive cardioplegia if retrograde cardioplegia is used in addition to antegrade cardioplegia. We conclude that by combining both antegrade and retrograde cardioplegia, there is a potential for enhanced overall microvascular perfusion.

Spontaneous closure of fenestrations in an interatrial Gore-Tex patch: application to the Fontan procedure.

The concept of the partial Fontan procedure, first described with the adjustable atrial septal defect (ASD) and more recently with the fenestrated technique, has become an accepted approach for the management of high-risk patients undergoing the Fontan procedure. Experience with both techniques has shown that a patent ASD placed in a prosthetic interatrial baffle may close spontaneously over a period of weeks to months. The mechanism and timing of spontaneous closure, as well as the effect of antiplatelet therapy on this process, are poorly understood. To better define this process, the interatrial septum of 15 mongrel dogs was excised and replaced with a fenestrated Gore-Tex (W.L. Gore, Flagstaff, AZ) patch. Postoperative echocardiography confirmed the patency of the ASD and left-to-right shunting. Animals were sacrificed 4 to 6 weeks postoperatively, or sooner if infection or other postoperative complications developed. Eight animals underwent no antiplatelet or anticoagulation therapy postoperatively, and 7 received antiplatelet therapy with aspirin. Patches were removed at the end of the study period and analyzed. By 6 weeks, all 2.7-mm and 4-mm holes had closed spontaneously in all animals that had not received antiplatelet therapy. The earliest closure occurred at 1 week. With antiplatelet therapy, hole closure was found to be delayed but not prevented, and was complete by 6 weeks in all but 1 animal. Histologic examination of the explanted patches revealed that closure was accomplished primarily through the ingrowth of fibrous tissue, accompanied by an inflammatory cell infiltrate.(ABSTRACT TRUNCATED AT 250 WORDS)

Perfluorochemical reperfusion yields improved myocardial recovery after global ischemia

Reperfusion injury remains a limiting factor in extending ischemic storage time for human heart transplantation. In this study, initial myocardial reperfusion with an oxygenated perfluorochemical (Fluosol) was investigated as a means of limiting such injury. Neonatal piglet hearts were arrested with crystalloid cardioplegia, excised, and stored for 12 hours in saline solution at 0 degrees C. Initial reperfusion (10 minutes) was either with whole blood (n = 6), unmodified perfluorochemical (n = 8), or aspartate/glutamate-enriched perfluorochemical cardioplegia (n = 6), and was followed by an additional 40 minutes of whole blood perfusion. Functional evaluation was then completed, and left ventricular biopsy specimens were taken. A control group (n = 7) was evaluated without an intervening period of ischemia. At a left ventricular end-diastolic pressure of 9 mm Hg, hearts stored in whole blood cardioplegia developed a left-ventricular stroke work index of 3.8 +/- 2.3 x 10(3) erg/g (mean +/- standard error of the mean). Under the same conditions, perfluorochemical-reperfused hearts achieved a stroke work index of 14.6 +/- 1.3 x 10(3) erg/g, significantly greater than that of the whole blood group (p < 0.001). Stroke work index for hearts reperfused with aspartate/glutamate-enriched perfluorochemical cardioplegia was 19.8 +/- 1.6 x 10(3) erg/g, significantly increased over that of the nonenriched perfluorochemical group (p < 0.01) and not different from values obtained in controls (19.2 +/- 0.8 x 10(3) erg/g).(ABSTRACT TRUNCATED AT 250 WORDS)

Fluosol cardioplegia results in complete functional recovery: A comparison with blood cardioplegia

Blood cardioplegia is considered by many to be the preferred solution for myocardial protection. Proposed benefits include the ability to deliver oxygen and the ability to maintain metabolic substrate stores. However, the decreased capacity of blood to release oxygen at hypothermic conditions as well as the presence of deleterious leukocytes, platelets, and complement may limit complete functional recovery. Fluosol is an asanguineous solution with the ability to bind and release oxygen linearly at low temperatures. Neonatal piglet hearts (24 to 48 hours old) were excised and supported on an isolated, blood-perfused working heart model. After baseline stroke-work index was determined, hearts were arrested with either normocalcemic blood cardioplegia (group 1, n = 8) or normocalcemic Fluosol cardioplegia (group 2, n = 8). Cold cardioplegia was administered at 45 mm Hg every 20 minutes for 2 hours. Hearts were then reperfused with whole blood. Functional recovery, expressed as percent of control stroke-work index, was determined 60 minutes after reperfusion at left atrial pressures of 3, 6, 9, and 12 mm Hg. Functional recovery at 60 minutes was similar between group 1 (95%, 93%, 93%, 88%) and group 2 (100%, 94%, 94%, 95%) at left atrial pressures of 3, 6, 9, and 12 mm Hg, respectively. Mean lactate consumption 5 minutes after reperfusion was significantly greater (p = 0.0001) in group 1 (31.8 +/- 6.3 micrograms.min-1 x g-1) than in group 2 (-0.59 +/- 0.1 microgram.min-1 x g-1), indicating superior metabolic recovery in the blood cardioplegia hearts. Edema formation, as determined both by water content (group 1, 81.10%; group 2, 81.63%) and by electron microscopy, was not significantly different between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Perfluorochemical Reperfusion Limits Myocardial Reperfusion Injury After Prolonged Hypothermic Global Ischemia

The ability of an oxygenated perfluorochemical (Fluosol) to limit myocardial reperfusion injury following global hypothermic ischemic insult was investigated. Neonatal piglet hearts were arrested with cold crystalloid cardioplegia and stored for 12 hours in 2 degrees C saline. Reperfusion was carried out using an isolated, blood-perfused, working heart preparation. Hearts were initially reperfused (10 minutes) with either whole blood (WB, n = 6), unmodified perfluorochemical (PFC, n = 8), or aspartate/glutamate-enriched perfluorochemical cardioplegia (PFC+, n = 6), prior to institution of whole blood perfusion, functional evaluation and left ventricular biopsy. A control group (C, n = 7) was evaluated without an intervening period of ischemia. At a left ventricular diastolic pressure of 9 mm Hg WB hearts developed a left-ventricular stroke work index (SWI) of 3.8 +/- 2.3 x 10(3) erg/g (mean +/- standard error of the mean). Under similar conditions, PFC-reperfused hearts achieved a SWI of 14.6 +/- 1.3 x 10(3), significantly greater than that of WB (p less than 0.001). SWI for PFC+ hearts was 19.8 +/- 1.6 x 10(3), significantly increased over that of PFC (p less than 0.01), and not different from values obtained for C (19.2 +/- 0.8 x 10(3)). In addition, PFC-reperfused hearts demonstrated superior maintenance (p less than 0.05) of ATP (2.08 +/- 0.16 umole/g), compared to WB (1.50 +/- 0.19), while preservation of ATP in PFC+ hearts (2.99 +/- 0.12), was significantly increased over that of PFC (p less than 0.001), and not significantly different from that for C (2.68 +/- 0.17).(ABSTRACT TRUNCATED AT 250 WORDS)

A Comparison of Distribution Between Simultaneously or Sequentially Delivered Antegrade/Retrograde Blood Cardioplegia

Abstract Commercially available cardioplegia delivery systems now allow for antegrade (aortic root, coronary ostia, saphenous vein graft) perfusion to occur either sequentially or simultaneous with retrograde (coronary sinus) perfusion. This study was designed to compare the total flow and local distribution of sequential versus simultaneous antegrade/retrograde cardioplegia delivery. Methods: Explanted human hearts diagnosed with idiopathic cardiomyopathy underwent a cold cardioplegic arrest and bicaval cardiectomy. Thirty‐seven degree centigrade blood cardioplegia containing colored microspheres was then delivered antegrade (red color) at a pressure of 80 mmHg or retrograde (blue color) at a pressure of 40 mmHg. In the sequential group (n = 6), cardioplegia was delivered antegrade and then retrograde for 2 minutes, respectively. For the simultaneous group (n = 6), cardioplegia was delivered both antegrade and retrograde for 2 minutes. The ventricular myocardium was then sampled at 12 representative sites to determine regional cardioplegic flow. Results: Mean total cardioplegia delivery/minute was 0.69 ± 0.62 mL/g per minute for sequential cardioplegia, and 0.46 ± 0.19 mL/g per minute for simultaneous cardioplegia (p > 0.05, NS). At the 12 ventricular sites sampled, mean regional cardioplegic flow (mL/g per min) was in general slightly greater for sequential delivery. However, this was not statistically significant (p > 0.05, NS). Conclusion: The data suggest that there may be a slight advantage in total cardioplegia delivery and regional cardioplegia delivery when using sequential rather than simultaneous cardioplegia delivery. However, this difference was not statistically significant and is likely not of clinical significance. Therefore, we would recommend using either sequential or simultaneous antegrade/retrograde cardioplegia based upon whichever technique facilitates the conduct of the individual operation.

Improved neonatal heart preservation with an intracellular cardioplegia and storage solution.

The optimal conditions for preservation of the neonatal heart for transplantation remain uncertain. An isolated, working neonatal piglet heart model was used to compare a standard extracellular-like cardioplegic solution followed by storage at 4 degrees C in normal saline for 12 hr (n = 8) to cardioplegia and storage at 4 degrees C for 24 hr in an intracellular-like solution (n = 7). Seven of eight hearts in the 12-hr Extracellular Group failed to regain function, with a maximum stroke work index (SWI), developed at a left ventricular end-diastolic pressure (LVEDP) of 9 mm Hg of 0.91 +/- 0.30 x 10(3) erg/g (mean +/- standard error of the mean), 7.1% of nonpreserved control hearts. In contrast, all hearts arrested and stored for 24 hr in the intracellular solution regained function with a maximum SWI, again at a LVEDP of 9 mm Hg of 9.51 +/- 1.98 X 10(3) erg/g, 73.7% of control (P less than 0.05). Ultrastructural changes seen by electron microscopy paralleled the functional results. We conclude that an intracellular arrest and storage solution may be superior to conventional solutions for extended preservation of the neonatal heart.