Response of the left ventricular connective tissue to hypoxia

Genovese, Arturo; Latte, Salvatore; Bozzaotre, Mariano; Chiariello, Massimo

doi:10.1007/bf01851776

Cited by 7 publications

(9 citation statements)

References 18 publications

(16 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Endurance conditioning causes the SRM to induce angiogenesis that reduces vascular resistance, increases ejection fraction (which lowers resting heart rate), and increases exercise capacity [28][29][30][31][32][33][34]. Distress is SRM hyperactivity that exhausts Factors VII, VIII, IX and X, tissue factor, von Willebrand Factor, ATP, fibrinogen, vitronectin, and fibronectin, and produces harmful or defective excesses of thrombin, soluble fibrin, and insoluble fibrin [35][36][37][38][39][40][41][42][43]. Distress is synonymous with disease.…”

Section: Stress Theory and The Srmmentioning

confidence: 99%

A Stress Repair Mechanism That Maintains Vertebrate Structure During Stress

Coleman

2010

CHDDT

View full text Add to dashboard Cite

Based on Capillary Gate Theory and Tissue Repair Theory, this paper describes the "Stress Repair Mechanism" (SRM) that maintains and repairs vertebrate tissues. It accounts for most of the mysterious manifestations of allostasis that remain unexplained by Hypothalamic-Pituitary-Axis (HPA) hormones and thereby enables the Universal Theory of Medicine predicted by Hans Selye. SRM activity explains hemodynamic physiology, capillary hemostasis, infarction, Korotkoff sounds, blood pressure, hypertension, diabetes, allostasis, allostatic load, anesthesia, analgesia, atherosclerosis, apoptosis, malignancy, eclampsia, sepsis, Multi-System Organ Failure (MSOF), the surgical stress syndrome, the fight or flight response, and numerous other manifestations of physiology and pathology. SRM function comprises the autonomic nervous system, the vascular endothelium, and the dynamic enzymatic interaction of blood-borne hepatic Factors VII, VIIIC, IX and X that produces thrombin, soluble fibrin and insoluble fibrin, whose combined effects account for all SRM manifestations. The vascular endothelium is a diaphanous neuroendocrine organ that lines all blood vessels and is the sole constituent of capillary walls. It secretes tissue factor into extravascular tissues, and insulates those tissues from the hepatic enzymes, so that tissue disruption exposes tissue factor to the enzymatic interaction and activates tissue repair. The vascular endothelium also releases nitric oxide and von Willebrand Factor into blood in accord with autonomic balance to regulate the enzymatic interaction to govern tissue perfusion and organ function. Therefore, continuously fluctuating combinations of nervous stimuli that affect autonomic balance and forces that disrupt tissues determine SRM activity.

show abstract

Section: Stress Theory and The Srmmentioning

confidence: 99%

A Stress Repair Mechanism That Maintains Vertebrate Structure During Stress

Coleman

2010

CHDDT

View full text Add to dashboard Cite

show abstract

“…Major candidate mechanisms that may account for cardiac fibroblast activation in coronary artery disease and HF are mechanical stimuli (fibroblasts as mechanoreceptors, reviewed in references 81 and 83) and local hypoxia (fibroblast as O 2 sensors, reviewed in reference 84–86). The myocardium undergoing ischemic (hypoxic) systolic bulging creates conditions for early fibroblast activation by sensing both mechanical and hypoxic stimuli.…”

Section: Microanatomy Of Scdmentioning

confidence: 99%

“…Further, perivenular (end capillary) adventitial fibroblasts are strategically positioned to detect local hypoxic distress, and their subsequent activation might invite perivascular fibrosis. The stimulation of fibrogenic responses by hypoxia in myocardium, kidney, skin, and other organs has been well recognized for many years 86 . Recently, multiple genes involved in matrix protein deposition have been recognized to be under regulation of the HIFs, a finding explaining the phenomenon of hypoxic fibrosis.…”

Section: Microanatomy Of Scdmentioning

confidence: 99%

Structural Pathways and Prevention of Heart Failure and Sudden Death

Pacifico

Henry

2003

Cardiovasc electrophysiol

View full text Add to dashboard Cite

We review the macroscopic and microscopic anatomy of myocardial disease associated with heart failure (HF) and sudden cardiac death (SCD) and focus on the prevention of SCD in light of its structural pathways. Compared to patients without SCD, patients with SCD exhibit 5‐ to 6‐fold increases in the risks of ventricular arrhythmias and SCD. Epidemiologically, left ventricular hypertrophy by ECG or echocardiography acts as a potent dose‐dependent SCD predictor. Dyslipidemia, a coronary disease risk factor, independently predicts echocardiographic hypertrophy. In adult SCD autopsy studies, increases in heart weight and severe coronary disease are constant findings, whereas rates of acute coronary thrombi vary remarkably. The microscopic myocardial anatomy of SCD is incompletely defined but may include prevalent changes of advanced myocardial disease, including cardiomyocyte hypertrophy, cardiomyocyte apoptosis, fibroblast hyperplasia, diffuse and focal matrix protein accumulation, and recruitment of inflammatory cells. Hypertrophied cardiomyocytes express “fetospecific” genetic programs that can account for acquired long QT physiology with risk for polymorphic ventricular arrhythmias. Structural heart disease associated with HF and high SCD risk is causally related to an up‐regulation of the adrenergic renin‐angiotensin‐aldosterone pathway. In outcome trials, suppression of this pathway with combinations of beta‐blockers, angiotensin‐converting enzyme inhibitors, angiotensin‐II receptor blockers, and mineralocorticoid receptor blockers have achieved substantial total mortality and SCD reductions. Contrarily, trials with ion channel‐active agents that are not known to reduce structural heart disease have failed to reduce these risks. Device therapy effectively prevents SCD, but whether biventricular pacing‐induced remodeling decreases left ventricular mass remains uncertain. (J Cardiovasc Electrophysiol, Vol. 14, pp. 764‐775, July 2003)

show abstract

“…The overall effect of hypoxia on collagen deposition is, however, best assessed in the intact heart. In this regard, non-ischemic hearts of rats exposed to IHH (18 h/day for 10 days to a barometric pressure of 0.4 atm (308 mmHg) and PO 2 of 64.5 mmHg [equivalent to 7,000 m altitude]) displayed an increase in myocardial collagen content as reflected by a doubling in the hydroxyproline content of the left ventricle [3].…”

mentioning

confidence: 99%

“…The obvious difference between the two protocols that may contribute to the seemingly discrepant outcomes is the assessment of collagen content in normally perfused hearts [3] versus hearts subjected to permanent coronary artery ligation [28]. This may imply that IHH has a differential, biphasic effect on collagen deposition in noninfarcted normally perfused regions of the heart versus scar, possibly due to the superimposition of an intermittent hypoxic stimulus on a region of the heart rendered chronically hypoxic by coronary artery occlusion.…”

mentioning

confidence: 99%