Acute rejection after cardiac transplantation: detection by interstitial myocardial pH

Intramyocardial pH was assessed as a potential marker for clinical evaluation and treatment of acute rejection following cardiac transplantation. Fifteen cats underwent forty operative procedures. Following intra-abdominal heterotopic heart transplantation, serial laparotomies were performed in the early (days 0 to 2), intermediate (days 5 to 7), and late (days 7 to 16) postoperative periods. Rejection was assessed by serial clinical examinations, ECG analyses, B-mode echocardiography, histological and ultrastructural analyses, and measurements of interstitial myocardial pH. Intramyocardial pH was measured by a new miniature (0.6 X 3.0 mm) fiberoptic pH transducer. At confirmed rejection, concomitant laparotomy and thoracotomy were performed and pH sensors were implanted in both native (anatomical) and graft hearts. Nine animals at rejection were given methylprednisolone and changes in graft and native heart pH were measured. The pH during absence of rejection, mild acute rejection, and severe acute rejection averaged 7.430 +/- 0.019, 7.233 +/- 0.040 (p less than .02), and 6.860 +/- 0.066 (p less than .02), respectively (mean +/- standard error of the mean). A progressive decline in pH was noted in each heart. In animals receiving steroids, graft heart pH increased over 90 minutes from 6.852 +/- 0.065 to 7.043 +/- 0.077 (p less than .05). Although pH decline may be secondary to either inflammatory or ischemic etiology, histological and ultrastructural analyses demonstrate a predominant inflammatory response with progressive mononuclear cell infiltration, interstitial edema, vascular wall edema, infiltration by polymorphonuclear neutrophil leukocytes, vacuolation of sarcoplasmic reticulum, and disarray of myocytes associated with falling pH. Degree of pH change correlated closely with degree of histological rejection, presence of ECG voltage decline, and change in wall thickness by ultrasound.