The involvement of mitochondrial dysfunction in many pathophysiological conditions and human diseases is well documented. In order to evaluate mitochondrial function in vitro,many experimental systems have been developed. Nevertheless the number of in vivo monitoring systems for the evaluation of mitochondrial activities in intact animals and patients is relatively limited. The pioneering development of the conceptual and technological aspects ofmitochondrial monitoring, in vitro and in vivo, was done by the late Prof. Britton Chance (July 24, 1913-November 16, 2010) since the early 1950s. It was my privilege to join his laboratory in 1972 and collaborate with him for almost four decades. The main achievements of our collaboration are presented in this paper. Our activities included cycles of technology development, followed by its applications to study various pathophysiological conditions. In the initial stage, the first fiber-optic-based NADH fluorometer was developed. This device enabled us to monitor various organs in anesthetized animals aswell as the brain of nonanesthetized small animals. Later on, the addition of various physiological parameters to NADH monitoring enabled us to correlate mitochondrial function with other cellular functions. The application of the developed technology to clinical situations was a major interest of Prof. Chance and indeed this goal was achieved in the last decade.As of today, the basic tool forNADHmonitoring and the large database of results are available for large-scale experimental and clinical applications.

Severe body stress induced by hypoxemia and hypotension may lead to total body energy state deterioration. The perfusion of the most vital organs is maintained at the expense of “less vital” organs. In the present study, we used a multi-site multiparametric (MSMP) monitoring system for real-time evaluation of tissue blood flow (TBF) and mitochondrial NADH fluorescence of the brain and the small intestine following hemorrhage. In Group 1, uncontrolled hemorrhage, mean arterial pressure (MAP) was decreased to 40mmHg within 2 minutes and shed blood was re-infused after 30minutes. In Group 2, controlled hemorrhage, during the 30minutes of hemorrhage, MAP was kept at 40mmHg. During hemorrhage, in both groups, the intestinal TBF and NADH deteriorated, while the brain remained relatively well protected. In Group 1, all parameters partly recovered within the hemorrhage phase, while in Group 2, complete recovery occurred only after resuscitation. At the end of the experiment, both models showed a decrease in intestinal viability (TBF decreased, NADH increased), while the brain metabolic state in Group 2 declined slightly. Our unique multi-parametric monitoring device demonstrated that, under hemorrhage, the small intestine responded entirely differently from the brain. This may suggest the potential usefulness of the monitoring of less vital organs, as proxy organs, in critical conditions such as massive hemorrhage. The present study also highlights the importance of mitochondrial function monitoring in similar conditions in the clinical environment.