Kumar, Mahesh

Coronary microvascular dysfunction (CMD) is increasingly recognized as a central mechanism underlying myocardial ischemia, heart failure with preserved ejection fraction, and adverse cardiovascular outcomes in patients with and without obstructive coronary artery disease. The coronary microcirculation plays a critical role in regulating myocardial perfusion through tightly coordinated myogenic, metabolic, and endothelial pathways. Disruption of these mechanisms results in impaired vasodilatory capacity, abnormal coronary flow reserve, and microvascular ischemia. This review summarizes the anatomy and physiology of coronary microcirculation and examines the pathophysiologic mechanisms driving CMD, including endothelial dysfunction, structural remodeling, inflammation, and neurohormonal dysregulation. Contemporary diagnostic strategies are reviewed, with emphasis on invasive coronary function testing and advanced noninvasive imaging modalities such as positron emission tomography and cardiac magnetic resonance imaging. The clinical implications of CMD across diverse disease states, including ischemia with nonobstructive coronary arteries, heart failure, and cardiomyopathies, are discussed. Finally, current therapeutic approaches, prognostic considerations, and emerging research directions aimed at improving diagnosis and targeted treatment of CMD are highlighted.

Shock is a life-threatening state of circulatory failure characterized by inadequate tissue oxygen delivery and cellular hypoxia. Lactate has emerged as a central biomarker in the diagnosis, risk stratification, and management of shock, yet its interpretation is complex and context dependent. Although traditionally viewed as a marker of anaerobic metabolism and tissue hypoperfusion, hyperlactatemia in distributive shock, particularly sepsis, frequently reflects multifactorial mechanisms, including increased aerobic glycolysis, adrenergic stimulation, mitochondrial dysfunction, and impaired hepatic clearance. This review examines the pathophysiology and classification of shock, the biochemical basis of lactate production and clearance, and the prognostic significance of both static lactate levels and lactate kinetics. We synthesize evidence supporting lactate as a robust prognostic marker while highlighting limitations of lactate-targeted resuscitation strategies. Emerging data favor multimodal approaches integrating lactate trends with complementary perfusion markers such as capillary refill time and central venous oxygen saturation. Lactate should be interpreted as one component of a comprehensive physiological assessment rather than an isolated therapeutic target.