The Age Factor In The Production Of Various Experimental Cardiopathies

Selye, Hans; Bajusz, E

doi:10.1093/geronj/14.2.164

Cited by 10 publications

(19 citation statements)

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“…89,91 It is now well established that myofibrillar degeneration is the hallmark signature lesion of specific catecholamine-induced myocardial necrotic injury. [89][90][91] This lesion is found at autopsy very consistently in patients in association with every form of ischemic cardiac disease, particularly in patients with SCD or AMI [89][90][91] where it is seen together with the classic coagulation necrosis typical of AMI, 10 as well as in patients dying after cardiovascular surgery. 91 This probably reflects the general stress response to cardiac surgery, particularly coronary bypass, where cardiac sympathetic nerves are disturbed and cut during the procedure.…”

Section: Myofibrillar Degeneration 89-91mentioning

confidence: 99%

“…Focus in the 20th century was compulsively centered on the attractive but simplistic idea that coronary vascular obstruction by CAD and thrombosis obstructing coronary blood flow was the sole putative cause and effect basis for IsHD. The fact that they usually but do not necessarily coexist 15,[103][104][105][106][107][108][109][110][111][112][113][114][115][116][117][118] has obscured their parallel (but independent) responses to neurovascular sensitivity to adrenergic vasoconstrictor actions 15 and adrenergic hypermetabolic actions, [8][9][10][11][12] as well as interactions with lipid metabolism [119][120][121][122][123][124][125] that concomitantly cause both IsHD and CAD together with its complications like angina pectoris, myocardial infarction, arrhythmias, SCD, and pathologic adrenergic remodeling of the myocardium. 2,10,73,74,79 In fact, the US Food and Drug Administration recently approved a test to measure the enzyme lipoprotein-associated phospholipase A2 (Lp-PLA2), which is considered to be an early indicator of so-called CAD.…”

Section: Introductionmentioning

confidence: 99%

“…believe that a rise in the levels of this enzyme will turn out to be a manifestation of catecholamine-induced activation of abnormal lipid metabolism, [119][120][121][122][123][124] which would be consistent with and appears to actually reflect AdHD, as discussed later. It now seems clear that CAD and IsHD can both be independently caused by abnormal adrenergic actions [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15]24, in the absence of CAD. 15,[103][104][105][106][107][108][109][110][111][112][113][114][115][116][117][118] Indeed, the concept of identifying AdHD as occurring independently of anatomic CAD clearly reconciles the contradictions inherent in the puzzle of IsHD and AMI occurring without associated obstructive CAD.…”

Section: Introductionmentioning

confidence: 99%

“…There is now overwhelming evidence of the role of neurohormone-driven sympathetic catecholamine-induced toxicity as a direct cause of cardiac necrosis, arrhythmias, CHF, atherosclerosis in general, [74][75][76][77][78][79][80]93,140 and CAD in particular. 2,10,74,79 This evidence has been obscured and ignored because the usual parallel occurrence of CAD together with IsHD has been widely, but mistakenly, interpreted as a putative cause-and-effect relationship, particularly enshrined when occluding thrombus is present, 74 which may itself be enhanced as a consequence of adrenergic actions causing coronary spasm and platelet aggregation. 15,20,25,26,47,55,[126][127][128][129] which traps platelet aggregates that facilitate thrombus formation.…”

Section: Introductionmentioning

confidence: 99%

“…[125][126][127][128][129] Catecholamines 125 and ADP accumulation during ischemia 126 both facilitate platelet aggregation, abnormal coronary reflex dynamics, and coronary vasospasm by releasing vasospastic substances, which further facilitates uptake of thrombin by platelets leading to thrombus formation. 74,[117][118][119][120][121][122][123][124][125][126][127][128][129][130] Most importantly, it is not commonly appreciated that catecholamines often cause an excessive increase in wasteful O 2 consumption, 3,4,[7][8][9][10][11] which can be blocked by sympathetic denervation 69 or pharmacologic adrenergic blockade (as shown in clinical study), and most effectively by down-regulation of the sympathetic nervous system by exercise, 10,11 which substantially increases cardiac efficiency and lowers myocardial O 2 consumption for any situation. 4 It is also not appreciated that catecholamines increase O 2 consumption (much of it wasteful) proportionately much more than an increase in cardiac work does.…”

Section: Introductionmentioning

confidence: 99%

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Prevention of Ventricular Fibrillation, Acute Myocardial Infarction (Myocardial Necrosis), Heart Failure, and Mortality by Bretylium

Bacaner

Brietenbucher²,

LaBree³

2004

American Journal of Therapeutics

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It is widely, but mistakenly, believed that ischemic heart disease (IsHD) and its complications are the sole and direct result of reduced coronary blood flow by obstructive coronary artery disease (CAD). However, cardiac angina, acute myocardial infarction (AMI), and sudden cardiac death (SCD) occur in 15%-20% of patients with anatomically unobstructed and grossly normal coronaries. Moreover, severe obstructive coronary disease often occurs without associated pathologic myocardiopathy or prior symptoms, ie, unexpected sudden death, silent myocardial infarction, or the insidious appearance of congestive heart failure (CHF). The fact that catecholamines explosively augment oxidative metabolism much more than cardiac work is generally underappreciated. Thus, adrenergic actions alone are likely to be more prone to cause cardiac ischemia than reduced coronary blood flow per se. The autonomic etiology of IsHD raises contradictions to the traditional concept of anatomically obstructive CAD as the lone cause of cardiac ischemia and AMI. Actually, all the signs and symptoms of IsHD reflect autonomic nervous system imbalance, particularly adrenergic hyperactivity, which may by itself cause ischemia as in rest angina. Adrenergic activity causing ischemia signals cardiac pain to pain centers via sympathetic efferent pathways and tend to induce arrhythmogenic and necrotizing ischemic actions on the cardiovascular system. This may result in ischemia induced metabolic myocardiopathy not unlike that caused by anatomic or spasmogenic coronary obstruction. The clinical study and review presented herein suggest that adrenergic hyperactivity alone without CAD can be a primary cause of IsHD. Thus, adrenergic heart disease (AdHD), or actually adrenergic cardiovascular heart disease (ACVHD), appears to be a distinct entity, most commonly but not necessarily occurring in parallel with CAD. CAD certainly contributes to vulnerability as well as the progression of IsHD. This vicious cycle, which explains the frequent parallel occurrence of arteriosclerosis and IHD, an association that appears to be linked by the same cause, comprises a common vulnerability to deleterious adrenergic actions on the myocardium, lipid metabolism, and vascular system alike, rather than viewing CAD and IsHD as having a putative cause and effect relationship as commonly thought. Adrenergic actions can also cause the abnormal lipid metabolism that is associated with CAD and IsHD by catecholamine-induced metabolic actions on lipid mobilization by activation of phospholipases. This may also be part of toxic catecholamine hypermetabolic actions by enhancing deleterious cholesterol and lipid actions in damaging coronary vessels by plaque formation as well as inducing obstructive coronary spasm and platelet aggregation. This may also cause direct toxic necrosis on the myocardium as well as atherosclerosis in blood vessels. In fact, drugs that inhibit adrenergic actions like propranolol, reserpine, and guanethidine all inhibit arteriosclerosis induced by hypercholestero...

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