Importance of primary percutaneous coronary intervention for reducing mortality in ST-elevation myocardial infarction complicated by out of hospital cardiac arrest.

BACKGROUND: Current recommendations are for primary percutaneous coronary intervention (pPCI) in ST-elevation myocardial infarction (STEMI) complicated by out of hospital cardiac arrest (OHCA). However, information about longer-term outcomes is sparse, particularly among high-risk patients who do not regain consciousness promptly after resuscitation. METHODS AND RESULTS: Of 1836 consecutive patients admitted with STEMI for pPCI between April 2008-October 2011, 132 (7.2%) who had suffered OHCA with recovery of spontaneous circulation (ROSC) form the study population. 101 patients survived to hospital discharge (76.5%) with only one further death in the first year. Prognosis was worse for the 62 patients who were unconscious on arrival and required admission to the intensive therapy unit (ITU), only 54% of whom survived. Every additional minute in the time to ROSC increased the hazard of death by 1.7% while alertness upon ROSC and successful reperfusion in response to pPCI reduced the hazard of death by 90% and 65% respectively. Full neurological recovery was recorded in 85.1% of those who survived to be discharged but in only 30.6% of the 34 survivors who were admitted unconscious and received ITU treatment. Every additional minute in the time to ROSC increased the odds of neurological deficit by 7.0%. CONCLUSIONS: In patients with STEMI who are conscious after OHCA, high rates of survival can be achieved with pPCI, depending in part on the time it takes for ROSC. Prognosis is less good in the subgroup brought to hospital unconscious but even in this high risk group neurologically intact survival can be achieved in about one-third of cases, suggesting the benefit of immediate pPCI in STEMI patients successfully resuscitated after OHCA.

Evidence for atrial natriuretic factor induced natriuretic peptide receptor subtype switching in rat proximal tubular cells during culture.

Culture and natriuretic peptide dependent changes in the expression of the natriuretic peptides atrial natriuretic factor (ANF), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) and the natriuretic peptide receptors A, B, and C in primary cultures of rat proximal tubular cells were demonstrated using polymerase chain reaction analysis and cyclic guanosine monophosphate response to ANF and CNP. Freshly isolated cells expressed mRNA coding for the natriuretic peptide receptor C only, with no expression of the natriuretic peptides or the natriuretic peptide receptors A or B. At confluence natriuretic peptide receptor C expression was lost, while mRNA transcripts for both ANF and BNP and the A and B receptors became apparent. The appearance of mRNA transcripts for the natriuretic peptide receptors A and B during cell growth correspond with a significant increase in the cyclic guanosine monophosphate response to both ANF and CNP, confirming the presence of functionally active guanylate cyclase linked A and B natriuretic peptide receptors. The observed changes in peptide receptor expression during culture were preceded by changes in natriuretic peptide mRNA expression, suggesting the possibility that natriuretic peptide receptor subtype switching may be under the control of endogenous peptide release. Incubation of freshly isolated proximal tubular cells with ANF, BNP, or CNP for 3 h induced similar changes in receptor expression. Incubation with ANF induced expression of the natriuretic peptide receptor B and CNP while inhibiting natriuretic peptide receptor C. Incubation with BNP induced expression of the natriuretic peptide receptor B and CNP. Incubation with CNP induced expression of the natriuretic peptide receptors A and B and CNP. These results suggest that primary cultures of rat proximal tubular cells may experience natriuretic peptide and natriuretic peptide receptor subtype switching as they approach confluence under the control of endogenously expressed natriuretic peptides.

Selective antagonism of the AT1 receptor inhibits angiotensin II stimulated DNA and protein synthesis in primary cultures of human proximal tubular cells.

The hypertrophy of renal proximal tubular cells occurs as an adaptive response to a variety of stimuli and may be involved with the progression of renal disease. Angiotensin II acting alone or in combination with other growth factors has been implicated in this process. The aims of this study were to identify the role of both angiotensin II and the angiotensin receptor subtypes in DNA synthesis and protein synthesis in human renal proximal tubular cells. Primary cultures of human renal proximal tubular cells were incubated with angiotensin II (10(-10) M, 10(-8) M, 10(-6) M) for 24 to 120 hours either alone or in combination with losartan, PD123319 or 8-bromo-cAMP. Incubation of human proximal tubular cells with angiotensin II (10(-10) M, 10(-8) M) induced a significant early increase in [3H]thymidine uptake by 19% and 56% (P < 0.01), respectively, and a later increase in total protein content by 30% (P < 0.01). The effect of angiotensin II upon DNA and protein synthesis was inhibited by 8-bromo-cAMP and losartan but not by PD 123319, indicating that the responses are mediated via the AT1 receptor and dependent upon the inhibition of adenylate cyclase.

Selective antagonism of the AT1 receptor inhibits the effect of angiotensin II on DNA and protein synthesis of rat proximal tubular cells.

The proliferation and hypertrophy of renal tubular cells are primary features in the progression of both acute and chronic renal disease often indicating a poor prognosis. Angiotensin II (ANG II), acting alone or in combination with other growth factors, has been implicated in this process. The aims of this study were to identify the importance of both ANG II and serum-derived factors upon cellular DNA synthesis and protein synthesis in renal proximal tubular cells and to identify the roles of the ANG II receptor subtypes in these processes together with the underlying intracellular signalling mechanisms involved. Primary cultures of renal proximal tubular cells were prepared from freshly isolated rat kidney cortex. Cells were cultured in either serum-replete Dulbecco's modified Eagle's/Ham's F12 or serum-deplete defined medium containing insulin, hydrocortisone, sodium selenite, transferrin, and tri-iodothyronine. Cells were incubated with ANG II (10(-10), 10(-8), 10(-6) M) for 24-120 h either alone or in combination with losartan, PD123319, or pertussis toxin. Incubation of proximal tubular cells in the presence of serum and ANG II (10(-8) M) induced a significant early (24 h) increase in DNA synthesis, together with a significant late (96 h) increase in protein content. [3H]thymidine uptake increased by 56% (p < 0.001) and total protein content by 23% (p < 0.05). In defined media, ANG II (10(-8) M) stimulated protein synthesis only. [3H]uridine uptake, [3H]leucine uptake, and total protein content increased by 25, 57, and 17% (p < 0.05), respectively. In both serum-replete and serum-deplete media, the effects upon protein synthesis of ANG II were inhibited by pertussis toxin and losartan, but not by PD123319. ANG II is clearly a potent stimulator of renal tubular cell DNA and protein synthesis-a response mediated via the AT1 receptor coupled to a pertussis toxin sensitive Gi protein.