The role of capillary transit time heterogeneity in myocardial oxygenation and ischemic heart disease

Abstract

Ischemic heart disease (IHD) is characterized by an imbalance between oxygen supply and demand, most frequently caused by coronary artery disease (CAD) that reduces myocardial perfusion. In some patients, IHD is ascribed to microvascular dysfunction (MVD): microcirculatory disturbances that reduce myocardial perfusion at the level of myocardial pre-arterioles and arterioles. In a minority of cases, chest pain and reductions in myocardial flow reserve may even occur in patients without any other demonstrable systemic or cardiac disease. In this topical review, we address whether these findings might be caused by impaired myocardial oxygen extraction, caused by capillary flow disturbances further downstream. Myocardial blood flow (MBF) increases approximately linearly with oxygen utilization, but efficient oxygen extraction at high MBF values is known to depend on the parallel reduction of capillary transit time heterogeneity (CTH). Consequently, changes in capillary wall morphology or blood viscosity may impair myocardial oxygen extraction by preventing capillary flow homogenization. Indeed, a recent re-analysis of oxygen transport in tissue shows that elevated CTH can reduce tissue oxygenation by causing a functional shunt of oxygenated blood through the tissue. We review the combined effects of MBF, CTH, and tissue oxygen tension on myocardial oxygen supply. We show that as CTH increases, normal vasodilator responses must be attenuated in order to reduce the degree of functional shunting and improve blood-tissue oxygen concentration gradients to allow sufficient myocardial oxygenation. Theoretically, CTH can reach levels such that increased metabolic demands cannot be met, resulting in tissue hypoxia and angina in the absence of flow-limiting CAD or MVD. We discuss these predictions in the context of MVD, myocardial infarction, and reperfusion injury.

Sialyltransferase7A, a Klf4-responsive gene, promotes cardiomyocyte apoptosis during myocardial infarction

“…1D-b). Given that MI induces a shortage in the oxygen supply to the cardiomyocytes [14,34], we examined the effect of hypoxia on Siat7A expression in vitro. Real-time PCR and immunoblotting as well as confocal microscopy analysis were performed using the cultured human cardiomyocyte cell line, AC16 (Fig.…”

Higher reticulocyte counts are associated with higher mortality rates in hemodialysis patients: a retrospective single-center cohort study

“…Several studies have reported an increased level of plasma EPO in patients with heart failure, which was correlated to a more severe outcome [10][11][12][13]. Meanwhile, female gender, inflammation, hyperphosphatemia, hyperglycemia, and dyslipidemia were identified as potential risk factors of microvascular dysfunction [14][15][16]. In postmenopausal women, microvascular dysfunction has been linked with adverse outcomes, such as Syndrome X [14].…”

“…The first is that the reticulocyte count could be a sensitive marker of tissue hypoxia. Reductions in tissue oxygen tension due to microvascular dysfunction would be expected to lead to the activation of hypoxia-inducible transcription factors [15], which in turn might initiate the production of EPO. EPO increases reticulocyte release from the bone marrow and therefore prolongs the maturation time of circulating reticulocytes; this is likely the reason for findings showing a high reticulocyte count [18].…”

Microcirculatory dysfunction and tissue oxygenation in critical illness

“…We extended the classical flow‐diffusion equation to take the biophysical effects of capillary transit time heterogeneity (CTH) into account and refer the reader to Jespersen and Østergaard22 and Østergaard et al 25. for details on the model and its application to brain and heart.…”

“…2 for the effects of reduced capillary volume and oxygen saturation) will reduce oxygen availability below the needs of normal tissue function. The figures for brain and heart were adapted from Jespersen and Østergaard22 and Østergaard et al 25…”