Assessment of hypothermia with a new "tympanic" thermometer.

OBJECTIVE: Rapid and accurate core temperature measurement is vitally important in trauma patients, especially in those with accidental hypothermia. We tested a new aural thermometer to measure "tympanic" temperatures and assessed its accuracy during normothermic and hypothermic cardiopulmonary bypass. METHODS: Tympanic, esophageal, and blood temperatures were compared in 10 patients undergoing open-heart surgery. In addition, the stability and reaction time of the tympanic thermometer was evaluated in 5 volunteers in a cold room, with and without facial fanning. RESULTS: We observed a good linear correlation between tympanic and esophageal (r = 0.96) and blood (r = 0.81) temperature measurements during normothermia and hypothermia. There was no evidence of iatrogenic ear lesions in any of the patients. In the cold-room tests, stability was excellent and the time for adjustment of tympanic temperature measurement was about 2 min (with and without facial fanning). CONCLUSION: The new tympanic thermoprobe is a simple, fast, and reliable device for measuring core temperature. The device was designed particularly for, and may be useful for, patients suffering from accidental hypothermia.

Experimental assessment of thrombogenicity in vascular prostheses before and during prostaglandin E1 treatment.

The effect of prostaglandin E1 (PGE1; Prostavasin), a powerful platelet blocking agent, was assessed on various new synthetic or biological prostheses in a 6-min in vivo extra corporal arterio-venous (AV) shunt. In eight anaesthetised and heparinised minipigs (weight 25.1 +/- 1.9 kg) the following materials were tested before and during PGE1 infusion (alprostadil-alpha-CD; 40 micrograms/50 ml NaCl/50 min or 0.8 microgram/min): PTFE, (Gore-tex, TW, 4 mm ID); Xenograft, Biologic (Solcograft, 5 mm ID), (non-porous) and Dacron (Atrium, 4 mm ID); polyurethane 1 (Braun-Melsungen, 4 mm ID); polyurethane 2 (S. Gogolewski, 4 mm ID), (porous). Technetium-labelled platelet deposition and blood flow were measured; morphology was assessed by scanning electron microscopy (SEM) and histology. Compared to control levels, PGE1 infusion had a significant systemic effect on mean arterial pressure required by the protocol (MAP 82.6 vs. 66.6 mm Hg; p < 0.001) and flow (173.6 vs. 134.8 mm/min; p < 0.001). Standardised platelet counts per area showed a marked overall decrease from 197 to 130 counts/min/mm2; NS). The morphological assessment by SEM showed a slight increase of surface cellular deposition (score: 6.7 vs. 8.3), the histology score being unchanged (3.9 vs. 3.7). Looking at deposition of platelets for each prosthesis, the porous materials showed a net improvement after PGE1 treatment as compared to non-porous materials. We conclude that PGE1 may be of benefit by reducing platelet deposition in synthetic porous vascular prostheses in the early phase.

Magnetic resonance spectroscopy for assessing myocardial rejection in the transplanted rat heart.

Traditionally, detection of heart rejection after heart transplantation is based on histologic grading of endomyocardial biopsy specimens. The value of magnetic resonance spectroscopy for determining heart rejection was assessed in rejecting and nonrejecting isografts and allografts using energy-rich phosphate spectroscopy. In 46 rats a heterotopic abdominal heart transplantation was performed, and animals were divided into the following groups: six isografts (no rejection), five untreated allografts (severe rejection), and 35 immunosuppressed allografts (mild to moderate rejection). One week after transplantation magnetic resonance spectroscopy was performed, and data were correlated to histologic findings (rejection grades according to Stanford and the New International Working Formulation classifications and relative volume of viable myocardium). Magnetic resonance spectroscopy allows detection of moderate to severe rejection with significant alterations in the energy-rich phosphates such as a decrease in the ratio of phosphocreatine/inorganic phosphate, phosphomonoester/inorganic phosphate, and beta-adenosine triphosphate/inorganic phosphate. A significant correlation was found between spectroscopic changes (phosphocreatine/inorganic phosphate) and histologic rejection (correlation coefficient r = 0.47, p < 0.005) and/or the amount of relative volume of viable myocardium and phosphocreatine/inorganic phosphate (r = 0.58) or beta-adenosine triphosphate/inorganic phosphate (r = 0.63), respectively. In conclusion magnetic resonance spectroscopy permits detection of moderate to severe degrees of heart rejection with a sensitivity of 85% and a specificity of 61%. Changes in the energy-rich phosphates correlate with the histologic grading of heart rejection and the relative volume of viable myocardium. Magnetic resonance spectroscopy appeared to be a valid technique for detecting myocardial rejection after heart transplantation in the reported experimental model.

Assessment of new immunosuppressive drugs in a rat cardiac allograft heterotopic model.

We assessed FK506 (FK) and rapamycin (RPM) in a heterotopic abdominal rat heart transplant model using a major histocompatibility mismatch (DA to LEW). The end point of our study was histologic grading of rejection (Billingham and working formulation) at 1 week. Two doses of FK (2.0 and 8.0 mg/kg p.o., q.d.) and RPM (1.5 and 6.0 mg/kg i.p., q.d.) were compared to allografts without and with ciclosporin (12.5 mg/kg p.o., q.d.) treatment. Results show: (1) weak heartbeat and full rejection on day 5 in all untreated allografts; (2) weak heartbeat and high degree of rejection in groups receiving low doses of FK and RPM; (3) strong heartbeat and mild rejection in both high FK and RPM dose groups comparable to the results of the hearts treated with ciclosporin; (4) 1 animal in each high FK and RPM dose group showed possible signs of toxicity, and (5) the strength of the heartbeat was not a reliable indicator of the efficacy of an immunosuppressive drug. We conclude that even in a major histocompatibility mismatch model at the time of the strongest immune response (1 week), all three tested drugs can reduce the degree of rejection from severe (untreated allografts) to mild if given in an adequate dosage.

Prevention of cardiac allograft rejection by FK506 and rapamycin: assessment by histology and nuclear magnetic resonance.

We assessed the effect of FK506 and rapamycin (RPM) in a heterotopic abdominal rat heart transplant model using a major histocompatibility mismatch (DA to LEW). The end-point of our study was the histologic grading of rejection (Stanford) and 31P magnetic resonance spectroscopy (MRS) at 1 week after transplantation. Two dosages of FK506 (2.0 and 8.0 mg/kg per os daily) and RPM (1.5 and 6.0 mg/kg intraperitoneally daily) were compared in allografts without and with cyclosporine (12.5 mg/kg per os daily) treatment. The results show: Weak heartbeat and full rejection at day 5 in all untreated allografts; severe rejection in groups on a low dose of FK506 and RPM; mild rejection in both high dose groups comparable to the results of the hearts treated with cyclosporine; MRS does not allow differentiation between no or mild forms of rejection. Energy-rich phosphates are near normal in the high dosage immunosuppression groups but show a significant reduction in the low dosage groups. We conclude that all three tested drugs can reduce the degree of rejection from severe (untreated allografts) to mild if given in an adequate dosage. MRS correlates well with the degree of histologic rejection but permits only the diagnosis of moderate or severe rejection.

Differentiation of cardiac ischemia and rejection by nuclear magnetic spectroscopy.

Nuclear magnetic resonance (NMR) criteria of early cardiac rejection are similar to those seen in myocardial ischemia, that is, a reduction of high energy phosphatases (Pc; ATP) and an increase of inorganic phosphates (Pi). Our aim was to assess in vivo changes of phosphorous spectroscopy (31P) induced by cardiac rejection and myocardial ischemia in the same animal. Heterotopic heart isografts (n = 5) and untreated allografts (n = 5) were examined at seven days on a two tesla wide-bore magnet with a surface coil. Subtotal global ischemia was produced for sequential NMR measurements, followed by heart excision for histological rejection grading (Billingham). Results 1. Isograft served as controls and showed normal energy-rich phosphate compounds and pH. 2. Rejecting (moderate to severe) allografts showed a decrease of Pc/Pi and beta-ATP/Pi ratio compared with isografts. However no significant pH drop could be detected. 3. Induced ischemia was confirmed by marked ECG-ST elevation and showed a significant early global myocardial acidosis (pH less than 6.9) particularly in severe prolonged ischemia (p less than 0.05). 4. Using 31P NMR techniques, ischemically induced changes were similar in isografts and allografts with a trend towards a more pronounced extent in the latter groups. In conclusion, magnetic resonance spectroscopy (31P and pH) allows in vivo differentiation between cardiac rejection and acute myocardial ischemia.