Infection-induced coronary dysfunction and systemic inflammation in piglets are dampened in hypercholesterolemic milieu

Abstract

The synergism of infection with conventional cardiovascular risk factors in atherosclerosis is much debated. We hypothesized that coronary arterial injury correlates with infection recurrence and pathogen burden and is further aggravated by hypercholesterolemia. Forty-two Göttingen minipigs were assigned to repeated intratracheal inoculation of PBS, Chlamydia pneumoniae (Cpn), or both Cpn and influenza virus at 8, 11, and 14 wk of age. Animals were fed either standard or 2% cholesterol diet (chol-diet). At 19 wk of age coronary vasomotor responses to acetylcholine (ACh) and adenosine were assessed in vivo and blood and tissue samples were collected. Nonparametric tests were used to compare the groups. In cholesterol-fed animals, total cholesterol/HDL was significantly increased in infected animals compared with noninfected animals [3.13 (2.17-3.38) vs. 2.03 (1.53-2.41), respectively; P = 0.01]. C-reactive protein (CRP) rose in infected animals [10.60 (4.96-18.00) vs. 2.47 (1.44-3.01) μg/ml in noninfected; P < 0.01] without significant difference between the mono- and coinfected groups. Among coinfected animals, both CRP and haptoglobin were lower in those fed chol-diet than in those fed standard diet (P < 0.05). The vasoconstricting response to ACh was most prominent in coinfected animals {769.3 (594-1,129) cm; P = 0.03 vs. noninfected [342 (309-455) cm] and P = 0.07 vs. monoinfected [415 (252.5-971.8) cm]}. Among monoinfected animals, similar to CRP, a trend for less vasoconstriction was observed in those fed chol-diet (P = 0.08). Coinfection of piglets appears to be associated with more pronounced coronary muscarinic vasomotor dysfunction. In monoinfected animals, use of chol-diet seems to dampen both coronary dysfunction and systemic inflammation induced by infection.

High Fat, Low Carbohydrate Diet Limit Fear and Aggression in Göttingen Minipigs

“…In another study where immature monkeys were fed a 40% fat (saturated, mono- and polyunsaturated), 40% carbohydrate diet, Kaplan and colleagues found that feeding supplementary cholesterol resulted in less aggression and more affiliative behaviour [17], suggesting a positive behavioural effect of cholesterol. In a pilot study, which was part of a larger study on early stage cardiovascular disease [18], Göttingen minipigs fed a standard minipig diet or a high fat/cholesterol diet also revealed differences in agonistic behaviour; the latter showing less aggression.…”

Coronary flow and reactivity, but not arrhythmia vulnerability, are affected by cardioplegia during cardiopulmonary bypass in piglets

“…In the present study, the coronary flow measurements were achieved using the Volcano Combomap® system, which has the advantage of assessing simultaneously both pressure and flow velocity (Figure 3/Panel A) via a 0.014″ coronary wire (Figure 3/Panel B). Our group has a certain expertise with using this device in the swine model [11,12]. …”

“…The coronary flow velocity study was performed before and 6–8 hours after completion of surgery [11,12]. After an intravenous bolus of 100 IU/kg heparin, a 4F short sheath was inserted into the right carotid artery and a 4F Judkins right coronary catheter was advanced into the ostium of the left coronary artery (LCA) under fluoroscopy guidance.…”

Neovascularization of coronary tunica intima (DIT) is the cause of coronary atherosclerosis. Lipoproteins invade coronary intima via neovascularization from adventitial vasa vasorum, but not from the arterial lumen: a hypothesis

“…induced visible atherosclerotic changes in chicken coronary arteries resembling that in humans, by infecting them with herpesvirus [8-10] and suggested the viral role in pathogenesis, a view shared by many scientists (for review see [11,12]). Mycoplasma pneumonia or Chlamydia pneumoniae infections alone [13] or together with influenza virus [14] have been proposed as contributory factors in the pathogenesis of atherosclerosis, and particularly by participation in obstruction of vasa vasorum [11]. However, these cases probably do not indicate the initiation of atherosclerosis, but are more likely to represent secondary infection of degenerating/necrotic tissue.…”

“…It should be emphasized that neither non-steroidal nor antibacterial anti-inflammatory treatments alter the risk of coronary atherosclerosis [15-18]. Despite the aforementioned studies [7-11,13,14], therefore, it can reasonably be claimed that no infectious cause of atherosclerosis has been demonstrated [19,20]. …”