The Cooling Effect of Coronary Blood Flow on Heart:
A New Approach

Coronary stenosis produces ischemia to the cardiac muscle by reducing blood flow. The anatomical and functional significance of coronary artery stenosis has been extensively studied.1,2 It is known that heat release is released from atherosclerotic plaques.3–6 Beating heart also produces energy leading to heat release, which is impaired in the presence of coronary artery disease (CAD). The impact of blood flow alterations, due to stenoses, on cardiac thermal homeostasis has not been elucidated. The aim of this study was to investigate whether acute interruption of blood flow may impair cardiac thermal homeostasis. In order to investigate the role of blood flow changes on cardiac thermal homeostasis we performed coronary sinus thermography using a new thermography catheter developed in our institution in subjects without significant atheromatic lesions, in which acute interruption of blood flow in left anterior descending artery was performed with balloon inflation. Methods Subjects evaluated for chest pain of recent onset without significant obstructive lesions were selected based on the absence of luminal narrowings. Patients with previous myocardial infarction, significant lesions (stenosis >= 50%), anemia, fever, thyroid disorders, arrhythmias, bradycardia, tachycardia, abnormal ejection fraction, valvular disease and hypoxemia were excluded. Patients treated with corticosteroids, other non-steroid anti-inflammatory agents except for aspirin or with active neoplastic or inflammatory disease were not enrolled. The study protocol was approved by the institutional ethical committee, and each patient provided written consent after being informed regarding the safety of the procedure based on previous experience with balloon-occlusion catheters of non-diseased segments.7 The investigation conforms with the principles outlined in the Declaration of Helsinki. Coronary sinus thermography catheter. The thermography catheter (7 Fr) was designed and developed in our Institution and was produced as a special product (Medispes SW A.G., ZUG, Switzerland) as previously described.8 A steering arm with a connector for the thermistor lead-wires is attached to the proximal part of the catheter. The steering arm passes through a lumen of the catheter and is attached to its tip. The distal 7 cm of the shaft of the catheter consist of a non-thrombogenic material. The thermistor lead-wires end to the connector and pass through another lumen of the catheter. A thermistor probe (temperature accuracy 0.05°C, time constant 300 ms, spatial resolution of 0.5 mm and linear correlation of resistance versus temperature over the range of 33–43°C, BetaTHERM, Ireland) is positioned at the tip of the catheter. Manipulation of the steering arm proximally enables the distal end of the catheter to be curved (0–180°; Figure 1). Data acquisition and processing has been previously described.4,8–10 Procedure. Coronary sinus thermography. The participants were in a fasted state without smoking for at least 12 hours before the study. The extent of coronary artery disease was evaluated angiographically and a prolonged recording of the venous phase was obtained for the positioning of the thermography catheter. Thereafter, the thermography catheter was advanced from the right femoral vein through an 8 Fr sheath. By manipulation of the steering arm at the proximal end, the distal end of the catheter was curved and the tip was positioned within the coronary sinus approximately 3 cm from the sinus orifice. Temperature measurements were performed 5 minutes after the last injection. Thereafter, the catheter was withdrawn into the mid-right atrium. Measurements of coronary sinus and right atrium blood were performed 3 consecutive times. Temperature recordings were stored in a computer. The mean blood temperature obtained in coronary sinus and right atrium was designated as temperature of the coronary sinus and right atrium respectively. Temperature difference (?T) was designated as: mean baseline blood temperature of right atrium subtracted from mean blood temperature of coronary sinus. Balloon inflation. A 7 Fr guiding catheter a 0.014-inch Doppler-tipped guidewire (Flowire, Cardiometricoronary Sinus, California) was advanced distally to left anterior descending artery. The instantaneous coronary flow velocity and the electrocardiogram were continuously displayed throughout the study and recorded on a videotape. Average peak velocity (APV) was derived automatically by the integrated signal-analyzing computer.2 A balloon-catheter was then introduced over the guidewire at the proximal segment of the vessel. A balloon sized according to the proximal reference vessel from the target segment, in which flow would be interrupted, was selected. The balloon was then progressively inflated until flow was completely interrupted. The balloon was dilated with a mixture of contrast medium and normal saline at 37°C (Figure 1). The balloon catheter was then deflated and withdrawn. Coronary sinus blood temperature was continuously recorded until 2 minutes after balloon deflation. C-reactive protein (CRP), troponin I, CK and CK-MB were measured in peripheral venous blood before the procedure. CRP was re-measured after 24 hours and cardiac enzymes at 6 and 12 hours. All patients underwent clinical follow-up at 12 months after the procedure. Reproducibility of measurements. In 5 subjects temperature was recorded at approximately 3–5 cm and at 7 cm from and at the ostium of coronary sinus. These measurements were performed three times. Distances and diameters were measured by quantitative coronary angiography (DCI-S, Automated Coronary Analysis, Philips, The Netherlands). Statistical Analysis. Continuous variables are presented as mean ± one standard deviation (SD) and qualitative variables as absolute and relative frequencies. Comparison of ?T at baseline, during and after balloon occlusion was performed by analysis of variance. Paired t-test was used for comparison of temperature between right atrium and coronary sinus. All P-values are two-sided and compared to a significant level of 5%. STATA 6 software was used (STATA Corporation, College Station, Texas). Results Eleven subjects without significant atherosclerotic obstructive lesions were studied. The baseline characteristics are presented in Table 1. Reproducibility. The 3 measurements obtained for determination of the coronary sinus blood temperature were constant in each patient (SD = 0-0.0335). Similar results were observed in right atrium blood temperature (SD = 0-0.0324). In subjects in which measurements were performed at 3 sites temperature was constant (SD = 0-0.02). Temperature measurements. The mean blood temperature was lower in right atrium compared to coronary sinus (38.08 ± 0.30 versus 38.19 ± 0.30?C, p Limitations. Heat production from heart was assessed by coronary sinus blood temperature. Although the rise of temperature was significantly increased acutely after coronary blood flow interruption, arterial blood temperature was not measured in order to estimate the arterial-venous temperature gradient. Moreover, simultaneous measurements in the right atrium and coronary sinus were not performed. However, previous studies have shown a strong correlation between arterial-venous temperature gradient and ?T.8 Considering that coronary sinus drains 85–96% of all veins arising from left ventricular and intraventricular septum and there are no other routes for venous blood drainage,17,18 the increase of coronary sinus temperature reflects the heat production from myocardium. The potential effect of collaterals or the Thebesian channels for venous drainage possibly underestimate the mentioned temperature differences, as the maximum heat production from myocardium is not measured. Moreover, the period of balloon dilatation was minimal for the activation of collateral flow. We selected this study population, in which a balloon dilatation was performed in order to acutely interrupt blood flow. The risk of low pressure balloon inflation in these subjects was extremely low, as has been demonstrated by balloon inflation in non-diseased segments with balloon-occlusion catheters.7 Indeed, angina was not mentioned and electrocardiographic changes or cardiac enzymes elevation was not detected. In addition, during a clinical follow-clinical implications. The results of this study showed that acute coronary blood flow interruption leads to increased heat production from the myocardium, demonstrating a possible cooling effect of coronary blood flow on cardiac muscle. Prolonged disturbance of cardiac cooling system may have severe unfavorable effects on coronary artery disease progression or precede the inflammatory process resulting in the destabilization of atherosclerotic plaques. In addition, the open-artery theory may be evaluated from the perspective of preserving thermal homeostasis after myocardial infarction, as chronic complete obstruction of flow may have detrimental effects. Moreover, by detecting the changes in coronary sinus temperature, appropriate drug administration may be administered targeting in maintaining cardiac thermal homeostasis. These hypotheses however need to be proved in future studies. Conclusion Acute blood flow obstruction in coronary arteries is associated with increased heat production from myocardium. The clinical impact of this mechanism needs to be further studied.

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