Andrea Vass

How Can Coronary Flow Reserve Be Altered by Severe Aortic Stenosis

The coronary flow reserve, a well‐known characteristic of the distensibility of the coronary arteries, can be measured by means of dipyridamole stress transesophageal echocardiography. This study compared the coronary flow reserve in patients with normal coronary arteries with aortic stenosis (Group 1), in patients with normal coronary arteries without aortic stenosis (Group 2), and in patients with significant left anterior descending coronary artery disease (Group 3). Patients and Methods: Groups 1 and 2 were comprised of 21 patients each, while Group 3 was comprised of 37 patients. Transesophageal stress echocardiography was carried out according to a standard protocol, with a vasodilator stimulus of dipyridamole in a dose of 0.56 mg/kg over 4 minutes. The coronary flow reserve was calculated as the ratio of posthyperemic to basal peak (CFR) and mean (mean CFR) diastolic flow velocities. Results: The left ventricular mass and left ventricular mass index were significantly higher in Group 1 than in Groups 2 and 3. The coronary flow reserve and the posthyperemic mean diastolic flow velocities were significantly lower, while the resting mean diastolic flow velocities were significantly higher in Groups 1 and 3 than in Group 2. Conclusions: In patients with aortic stenosis and a normal coronary angiogram, the coronary flow reserve is significantly lower, similarly as in the case of significant left anterior descending coronary artery disease. In severe aortic stenosis with left ventricular hypertrophy, stress transesophageal echocardiography is unable to distinguish between the drop in coronary flow reserve caused by a vascular or a myocardial component, and therefore, not suitable for the selection of patients with significant coronary artery disease, even in cases of left anterior descending coronary artery disease.

The coronary flow velocity reserve measured by stress transoesophageal echocardiography evaluates the success of coronary interventions - Results of a 5-year follow-up

Objectives. The aim of the present study was to examine the long-term prognostic value of coronary flow velocity reserve (CFR) evaluated by means of stress transoesophageal echocardiography (STEE) in patients who have undergone percutaneous coronary intervention (PCI). Design. The study comprised 31 patients with significant LAD stenosis who underwent LAD-PCI. In consequence of their clinical signs, 11 subjects required rePCI or coronary artery bypass graft (CABG) operation within six months. The clinical status of the remaining 20 cases improved during the follow-up. STEE examinations were performed before LAD-PCI and after it. Results. The CFR of patients in a stable clinical condition improved during the follow-up, while the CFR of those who required rePCI or CABG remained unchanged. From this patient population, two subjects died during the 5-year follow-up. Conclusions. Most of the patients who displayed an improved CFR after PCI suffered no major clinical events during the 5-year follow-up; in contrast, in those who a priori had a low CFR and did not show any improvement after PCI, major events did occur during this period.

Complement C5A antagonist treatment improves the acute circulatory and inflammatory consequences of experimental cardiac tamponade.

Objective:Cardiogenic shock often leads to splanchnic macro- and microcirculatory complications, and these events are linked to local and systemic inflammatory activation. Our aim was to investigate the consequences of complement C5a antagonist treatment on the early circulatory and inflammatory changes in a clinically relevant large animal model of cardiac tamponade. Design and Setting:A randomized, controlled in vivo animal study in a university research laboratory. Subjects:Anesthetized, ventilated, and thoracotomized Vietnamese mini pigs (24 ± 3 kg). Interventions:Group 1 (n = 6) served as sham-operated control. In group 2 (n = 7), cardiac tamponade was induced for 60 minutes by the administration of intrapericardial fluid, while the mean arterial pressure was kept in the interval 40 to 45 mm Hg. Group 3 (n = 6) was treated with a complement C5a antagonist compound (the peptide acetyl-peptide-A, 4 mg/kg) after 45 minutes of tamponade. Measurements and Main Results:The macrohemodynamics, including the superior mesenteric artery flow, was monitored; the average red blood cell velocity in the small intestinal mucosa was determined by an intravital orthogonal polarization imaging technique. The whole blood superoxide production, the plasma level of high-mobility group box protein-1 and big-endothelin and the small intestinal myeloperoxidase activity were measured. One hundred eighty minutes after the relief of tamponade, the mean arterial pressure was decreased, while the plasma levels of superoxide, high-mobility group box protein-1, and big-endothelin, and the intestinal myeloperoxidase activity were increased. The administration of acetyl-peptide-A normalized the mean arterial pressure and preserved the cardiac output, while the superior mesenteric artery flow and mucosal average red blood cell velocity were increased significantly, and the plasma superoxide, high-mobility group box protein-1, big-endothelin, and intestinal myeloperoxidase levels were reduced. Conclusions:These results provide evidence that blockade of the C5a effects significantly influences the acute splanchnic macro- and microhemodynamic complications and decreases the potentially harmful inflammatory consequences of experimental cardiogenic shock.

Inflammatory Activation after Experimental Cardiac Tamponade

Background/Purpose: Cardiac tamponade is a medical emergency situation associated with a high rate of life-threatening complications, even after immediate interventions. Our aim was to characterize the acute inflammatory consequences of this event in a clinically relevant large animal model. Methods: Cardiac tamponade was induced for 60 min in anesthetized, ventilated and thoracotomized minipigs by intrapericardial fluid administration, the mean arterial pressure (MAP) being maintained in the interval of 40-45 mm Hg (n = 8). A further group (n = 7) served as sham-operated control. The global macrohemodynamics, including the right- and left-heart end-diastolic volumes (RHEDV and LHEDV), the pulmonary vascular resistance index (PVRI) and the superior mesenteric artery (SMA) flow, were monitored for 240 min, and the intestinal microcirculatory changes (pCO2 gap) were evaluated by indirect tonometry. Blood samples were taken for the determination of cardiac troponin T and vasoactive inflammatory mediators, including histamine, nitrite/nitrate, big-endothelin, superoxide and high-mobility group box protein-1 levels in association with intestinal leukocyte and complement activation. Results: The cardiac tamponade induced significant decreases in MAP, cardiac output, LHEDV and SMA flow, while the PVRI and the pCO2 gap increased significantly. After the removal of fluid from the pericardial sac, the MAP and the LHEDV were decreased, while the PVRI and the pCO2 gap remained elevated when compared with those in the sham-operated group. In the posttamponade period, the abrupt release of inflammatory mediators was accompanied by a significant splanchnic leukocyte accumulation and complement activation. Conclusions: The macrocirculatory and splanchnic microcirculatory disturbances were accompanied by a significant proinflammatory reaction; endothelin and the complement system may be significant components of the inflammatory cascade that is activated in this porcine model of pericardial tamponade.

Circulatory consequences of reduced endogenous nitric oxide production during small-volume resuscitation.

Hypertonic small-volume resuscitation transiently restores the cardiovascular function during various circulatory disturbances. Nitric oxide (NO) is an important mediator of flow-induced peripheral and central hemodynamic changes, and therefore, we hypothesized that a decreased endogenous NO production could influence the consequences and the effectiveness of hypertonic fluid therapy. The main goal of this study was to outline and compare the circulatory effects small volume hypertonic saline-dextran (HSD, 7.5% NaCl-10% dextran; 4 ml/kg iv) infusion with (n=7) or without (n=7) artificially diminished NO production in normovolemic anesthetized dogs. HSD administration significantly increased cardiac index (CI), coronary flow (CF) and myocardial contractility, and elevated plasma nitrite/nitrate (NOx) and endothelin-1 (ET-1) levels. However, the late (2 h) postinfusion period was characterized by significantly decreased myocardial NO synthase (NOS) and enhanced myeloperoxidase activities. Pre-treatment with the non-selective NOS inhibitor N-nitro-L-arginine (NNA, 4 mg/kg) immediately increased cardiac contractility, and the HSD-induced CI and CF elevations and the positive inotropy were absent. Additionally, plasma ET-1 levels increased and NOx levels were significantly decreased. In conclusion, our results demonstrate that HSD infusion leads to preponderant vasoconstriction when endogenous NO synthesis is diminished, and this could explain the loss of effectiveness of HSD resuscitation in NO-deficient states.