Influence of chronic total occlusions on coronary artery bypass graft surgical outcomes.

BACKGROUND: Presence of epicardial coronary artery chronic total occlusion (CTO) predicts higher referral rates for coronary bypass graft surgery (CABG). However, the impact of coronary artery CTO on CABG outcomes has never been systematically studied. METHOD: We examined one-year outcomes in 605 consecutive Veterans, discharged post-CABG between June 2005 and December 2008. RESULTS: A coronary CTO was present in 256 patients (42%), predominantly (48.3%) in the right coronary artery distribution. Baseline clinical characteristics and medical therapy were similar in patients with and without a coronary CTO. A single CTO was present in 73.8%, and 26.2% patients had multiple CTO. All left anterior descending coronary artery CTO were successfully bypassed, as were >92% in left circumflex and right coronary arteries and 85% CTO in multiple coronary artery distributions. During the mean follow-up of 348.9 ± 4.5 days, incidence of all-cause death and myocardial infarction were similar in both groups (7.1% in CTO group and 7.4% in non-CTO group; p = 0.97). CTO >20 mm in length constituted 74.9% and >40 mm 37.8%. One-year survival post-CABG was significantly lower in patients with CTO lengths >40 mm compared to ≤20 mm (p = 0.04). CTO >40 mm was an independent predictor of post-CABG mortality controlling for age, number of CTO, comorbid diseases, clopidogrel use, severity of coronary artery disease, renal failure, and left ventricular ejection fraction. CONCLUSION: CABG achieves high success in grafting epicardial coronary vessels with CTO; however, presence of long coronary CTO (>40 mm) is an independent predictor of post-CABG survival.

Frequency, Indications, and Outcomes of Guide Catheter Extension Use in Percutaneous Coronary Intervention.

BACKGROUND: The frequency and outcomes of guide catheter extension use during percutaneous coronary intervention (PCI) have received limited study. METHODS: We retrospectively examined 1539 consecutive PCIs performed between May 2010 and November 2013 to determine the frequency and outcomes of guide catheter extension utilization. RESULTS: During the study period, a guide catheter extension was used in 83 cases (5.4%; 95% confidence interval, 4.3%-6.6%) in 86 vessels. The PCI target vessel was the left anterior descending artery (11%), circumflex (23%), right coronary artery (50%), left main (1%), or a saphenous vein bypass graft (15%). The indications for use (non-mutually exclusive) were to facilitate equipment delivery or provide vessel support/ engagement (84.7%), thrombus aspiration (10.5%), retrieval of lost devices (2.3%), facilitation of reverse controlled antegrade and retrograde tracking and dissection (1%), and selective vessel visualization with contrast (1%). Guide catheter extension success rate was 73.3% and technical and procedural success rates were 91.6% and 90.4%, respectively. Four patients (4.8%) experienced a guide catheter extension-related complication: vessel dissection/injury in 2 cases (1 case required emergency coronary artery bypass graft surgery and 1 case required stenting) and equipment loss in 2 cases (1 detachment of the distal guide-extension marker and 1 shearing of a guidewire tip that embolized to the renal artery). CONCLUSIONS: In a contemporary patient population undergoing PCI, a guide catheter extension was used in approximately 1 of 20 PCIs. Guide catheter extensions can facilitate procedural success, but also carry low risk for device-related complications.

Intratracheal mesenchymal stem cell administration attenuates monocrotaline-induced pulmonary hypertension and endothelial dysfunction.

The administration of mesenchymal stem cells (MSCs) has been proposed for the treatment of pulmonary hypertension. However, the effect of intratracheally administered MSCs on the pulmonary vascular bed in monocrotaline-treated rats has not been determined. In the present study, the effect of intratracheal administration of rat MSCs (rMSCs) on monocrotaline-induced pulmonary hypertension and impaired endothelium-dependent responses were investigated in the rat. Intravenous injection of monocrotaline increased pulmonary arterial pressure and vascular resistance and decreased pulmonary vascular responses to acetylcholine without altering responses to sodium nitroprusside and without altering systemic responses to the vasodilator agents when responses were evaluated at 5 wk. The intratracheal injection of 3 x 10(6) rMSCs 2 wk after administration of monocrotaline attenuated the rise in pulmonary arterial pressure and pulmonary vascular resistance and restored pulmonary responses to acetylcholine toward values measured in control rats. Treatment with rMSCs decreased the right ventricular hypertrophy induced by monocrotaline. Immunohistochemical studies showed widespread distribution of lacZ-labeled rMSCs in lung parenchyma surrounding airways in monocrotaline-treated rats. Immunofluorescence studies revealed that transplanted rMSCs retained expression of von Willebrand factor and smooth muscle actin markers specific for endothelial and smooth muscle phenotypes. However, immunolabeled cells were not detected in the wall of pulmonary vessels. These data suggest that the decrease in pulmonary vascular resistance and improvement in response to acetylcholine an endothelium-dependent vasodilator in monocrotaline-treated rats may result from a paracrine effect of the transplanted rMSCs in lung parenchyma, which improves vascular endothelial function in the monocrotaline-injured lung.

Angiotensin-(1-7) potentiates responses to bradykinin but does not change responses to angiotensin I.

Angiotensin-(1-7) (Ang-(1-7)), a bioactive peptide in the renin-angiotensin system, has counterregulatory actions to angiotensin II (Ang II). However, the mechanism by which Ang-(1-7) enhances vasodepressor responses to bradykinin (BK) is not well understood. In the present study, the effects of Ang-(1-7) on responses to BK, BK analogs, angiotensin I (Ang I), and Ang II were investigated in the anesthetized rat. The infusion of Ang-(1-7) (55 pmol/min i.v.) enhanced decreases in systemic arterial pressure in response to i.v. injections of BK and the BK analogs [Hyp3, Tyr(Me)8]-bradykinin (HT-BK) and [Phe8psi (CH2-NH) Arg9]-bradykinin (PA-BK) without altering pressor responses to Ang I or II, or depressor responses to acetylcholine and sodium nitroprusside. The angiotensin-converting enzyme (ACE) inhibitor enalaprilat enhanced responses to BK and the BK analog HT-BK without altering responses to PA-BK and inhibited responses to Ang I. The potentiating effects of Ang-(1-7) and enalaprilat on responses to BK were not attenuated by the Ang-(1-7) receptor antagonist A-779. Ang-(1-7)- and ACE inhibitor-potentiated responses to BK were attenuated by the BK B2 receptor antagonist Hoe 140. The cyclooxygenase inhibitor sodium meclofenamate had no significant effect on responses to BK or Ang-(1-7)-potentiated BK responses. These results suggest that Ang-(1-7) potentiates responses to BK by a selective B2 receptor mechanism that is independent of an effect on Ang-(1-7) receptors, ACE, or cyclooxygenase product formation. These data suggest that ACE inhibitor-potentiated responses to BK are not mediated by an A-779-sensitive mechanism and are consistent with the hypothesis that enalaprilat-induced BK potentiation is due to decreased BK inactivation.

Vasoactive prostanoids are generated from arachidonic acid by COX-1 and COX-2 in the mouse.

Generation of vasoactive prostanoids from arachidonic acid by cyclooxygenase (COX)-1 and COX-2 was investigated in anesthetized mice. Intravenous injections of the prostanoid precursor arachidonic acid increased pulmonary arterial pressure and decreased systemic arterial pressure. Pulmonary pressor and systemic depressor responses were attenuated by SC-560 and nimesulide, inhibitors of COX-1 and COX-2, in doses that did not alter responses to injected prostanoids. Pulmonary pressor responses to arachidonic acid were blocked and a depressor response was unmasked, whereas systemic depressor responses were not altered, by a thromboxane receptor antagonist. Pulmonary and systemic pressor responses to angiotensin II injections and systemic pressor responses to angiotensin II infusion were not modified by COX-1 or COX-2 inhibitors but were attenuated by losartan. Systemic depressor responses to arachidonic acid were smaller in COX-1 and COX-2 knockout mice, whereas responses to angiotensin II, norepinephrine, U-46619, endothelin-1, and PGE(1) were not different in COX-1 and COX-2 knockout and wild-type control mice. These results suggest that vasoactive prostanoids with pulmonary pressor and systemic vasodepressor activity are formed by COX-1 and COX-2 and are consistent with Western blot analysis and immunostaining showing the presence of COX-1 and COX-2. These data suggest that thromboxane A(2) (TxA(2)) is formed from the precursor by COX-1 and COX-2 in the lung and are in agreement with immunofluorescence studies showing thromboxane synthase. The present data suggest that COX-1- or COX-2-derived prostanoids do not modulate responses to angiotensin II or other vasoactive agents and that prostanoid responses are similar in CD-1 and C57BL/6 and in male and female mice.