Explosive Vomiting Associated with Proximal Colonic Distention during a Difficult Propofol-Assisted Colonoscopy.

We present a case of explosive vomiting associated with the extensive manipulation of the proximal colon during a difficult colonoscopy procedure. The cause of vomiting in this case may have been multifactorial; however, proximal colonic distention was the most likely factor because the onset of vomiting coincided with proximal colonic manipulation and happened without any prodromal signs, coughing, and airway obstruction. Propofol, the sedative most commonly administered to the patient during colonoscopy, allows for a deep state of sedation, and consequently extensive colonic distention and scope manipulation. Colonic distention may lead to a higher risk of vomiting. We reviewed the neurocircuitry associated with vomiting and discussed why proximal colonic distention may increase the risk of vomiting. We emphasize vigilance during the manipulation of the proximal colon because vomiting increases the potential for aspiration pneumonitis and pneumonia in patients under deep propofol sedation with attenuated airway responses.

An Unusual Cause of Failure to Ventilate.

We report an unusual case of endotracheal tube failure. It was due to a manufacturing defect in the internal white plastic piece that is normally depressed by the luer-lock syringe within the blue pilot balloon. Prior to use, the endotracheal tube was tested and functioned normally. A 64-year-old patient in the intensive care unit with a history of hypertension was being mechanically ventilated after uneventful abdominal surgery. After several hours in the intensive care unit, he was noted to be suddenly no longer receiving adequate tidal volumes from the ventilator. It was found that the cuff on the endotracheal tube was not retaining air when it was filled with air from a syringe. This lead to a large "leak" around the endotracheal tube such that the intended tidal volumes set on the ventilator were not delivered to the patient. The patient was uneventfully reintubated and did well. Subsequent investigation revealed the cause to be a manufacturing defect in the internal white plastic piece that is normally depressed by the luer-lock syringe within the blue pilot balloon. Other mechanisms of cuff failure are reviewed in this case report. This case is an unusual reason for cuff failure. Illustrations supplied alert the reader how to identify the appearance of this manufacturing defect in a pilot balloon. This case illustrates the potential device malfunctions that can develop during a procedure, even when the equipment has been tested and previously functioned well. Even small defects developing in well-engineered products can lead to critical patient care emergencies.

Varicella Pneumonia: Case Report and Review of a Potentially Lethal Complication of a Common Disease.

Varicella zoster virus causes varicella (chickenpox). It can be reactivated endogenously many years later to cause herpes zoster (shingles). Although varicella is usually a benign disease in healthy children, it resulted in over 11 000 hospitalizations and over 100 deaths every year, in all ages, in the United States. Morbidity was considerably worse in older teenagers and adults. Between 5% and 15% of cases of adult chickenpox will produce some form of pulmonary illness. Progression to pneumonia risk factors include pregnancy, age, smoking, chronic obstructive pulmonary disease, and immunosuppression. Typically, pulmonary symptoms occur 1 to 6 days after varicella zoster infection. They often include cough, fever, and dyspnea. Treatment is a 7-day course of intravenous acyclovir for varicella pneumonia. Early intervention may modify the course of this complication. This review illustrates practical features with a case of a 34-year-old female with severe varicella pneumonia. Despite the lack of significant past medical history and absence of immunosuppression, her pneumonia worsened and by using continuous positive airway pressure mask, intubation was avoided. More important, the radiographic progression of severe varicella pneumonia is shown. This highlights how a common disease of varicella can progress in an adult and manifest with significant organ malfunction.

Near-fatal kinking of mammary graft due to emphysematous lung disease.

Left internal mammary artery grafting is commonly used in elective coronary artery bypass graft surgery. We report a near-fatal case with graft kinking upon sternal closure due to distended, emphysematous lungs impinging on the mammary graft. After the sternum was closed, the patient suffered a severe hemodynamic deterioration. Surgical examination revealed kinking of his left internal mammary artery upon sternal closure due to distended, emphysematous lungs impinging on the mammary graft. Using an off-bypass technique, the kink in the mammary graft to the left anterior descending artery was removed by moving the origin of the left internal mammary artery to a hooded graft of a saphenous vein graft instead. In this position, the graft no longer was impinged upon by the distended emphysematous lungs. Subsequently, the patient's sternum was closed without hemodynamic impingement. Although chronic obstructive pulmonary disease is well described to increase complications in coronary artery bypass graft surgery, it has not been previously associated with the kinking of a left internal mammary artery. This report highlights another contribution that chronic obstructive pulmonary disease can make to increased morbidity following coronary artery bypass graft surgery and alerts readers to watch for this complication in susceptible patients.

Hospital initiatives in promoting smoking cessation: A 12-year follow-up.

In the present study, the availability of smoking cessation programs (SCP) was surveyed in the same randomly selected USA hospitals in 2000 and 2012. A total of 102 USA hospitals were randomly selected for this survey. Each hospital website was searched for the topic of smoking cessation. In the second phase of the survey, the main switchboard number of each hospital was anonymously telephoned and the 'stop smoking clinic' was requested. The phone survey results showed that the percentage of hospital switchboard calls that were connected to a SCP remained identical at 47% in 2000 and 2012. The results for the internet availability of SCP on hospital websites improved from 30% in 2000 to 47% in 2012. There were more hospitals that added additional SCP information (27%) compared with those that removed SCP information (15%) by 2012. Among the 57% of hospitals that showed no change in internet SCP information, 22% remained positive for such information while 35% remained negative. The phone survey of hospitals showed that 47% of USA hospitals were able to connect a caller to a SCP in the years 2000 and 2012. While there was no reduction over the 12 years, there was no increase in the percentage of hospital switchboards that connected to a SCP. Availability of SCP information on hospital web sites improved to a limited extent; increasing from 30% of sites in 2000 to 47% in 2012. Providing SCP on a hospital website is easy and free, for example adding a link to QuitNet or QuitLink. The present study adds to information gathered 12 years earlier, and is unusual in being able to provide follow-up data on the same set of hospitals studied previously.

Methylene blue treatment for cytokine release syndrome-associated vasoplegia following a renal transplant with rATG infusion: A case report and literature review.

Rabbit anti-thymocyte globulin (rATG) is an infusion of polyclonal rabbit-derived antibodies against human thymocyte markers, which can be used to prevent and treat acute rejection following organ transplantation. However, the product monograph issued by the manufacturer (Sanofi Canada) reports that serious immune-mediated reactions have been observed following the use of rATG, consisting of anaphylaxis or severe cytokine release syndrome (CRS), which is a form of vasoplegic syndrome (VS), in which distributive shock occurs refractory to norepinephrine (NE) and vasopressin (VP). Severe infusion-associated reactions are consistent with CRS and can cause serious cardiac or respiratory problems, or in certain cases, mortality. CRS is a form of systemic inflammatory response syndrome (SIRS). In SIRS, the substantial activation of endothelial inducible nitric oxide synthase (iNOS) and smooth muscle guanylate cyclase (GC) is observed, which can produce severe hypotension that is unresponsive to conventional vasopressors. Methylene blue (MB) is a direct inhibitor of iNOS and GC and has been used as an effective treatment for VS following cardiothoracic surgery. In the present study, the successful use of MB as a rescue therapy for CRS in a patient receiving rATG following a renal transplant was reported. Following an uneventful cadaveric kidney transplant involving the intravenous (IV) administration of rATG for the induction of immunological tolerance, the patient became markedly hypotensive and tachycardic. The patient required high doses of VP and NE infusions. Following the protocol described for treating refractory VS in post-cardiac surgery patients, the decision was made to initiate the patient on an IV MB infusion. This treatment protocol was shown to improve the hemodynamic status of the patient, which enabled the withdrawal of vasopressors and suggests an important role for methylene blue in the management of refractory VS.

A new technique for avoiding barotrauma-induced complications in apnea testing for brain death.

Prompted by our experience with complications occurring with apnea testing (AT), we discuss complications reported in the literature. AT is an integral part of brain death assessment. Many complications of AT have been described, including hypoxemia, arterial hypotension, tension pneumothorax and cardiac arrest. We conclude that a commonly used technique in conducting AT can create auto-positive end expiratory pressure (PEEP) and contributes to many complications. The mechanism of occult auto-PEEP in AT is discussed. Intensive care unit patients may have a compensated and asymptomatic relative hypovolemia that can be decompensated by a small amount of auto-PEEP produced by air trapping during insufflating oxygen (O2) through a 7.0 endotracheal tube (ETT). It could then lead to decreased preload, decreased stroke volume, decreased cardiac output and thus, to hypotension and a compensatory tachycardia. The placement of the standard O2 tubing (6mm outside diameter [OD]) inside the 7.0 ETT (7mm inside diameter [ID]) greatly decreased the ETT lumen (73%). We changed our practice to instead use readily available small pressure tubing to insufflate O2 for AT to avoid excessive reduction in the ETT lumen. The change from standard O2 tubing (6mm OD) to pressure tubing (3mm OD) will greatly decrease the reduction in cross-sectional area of 7.0 ETT lumen from 73 to 18% and avoid potential complications of air trapping, auto-PEEP and barotrauma. We have successfully used this new simple technique with readily available equipment to eliminate auto-PEEP in AT while preserving oxygenation.

Lower incidence of hypo-magnesemia in surgical intensive care unit patients in 2011 versus 2001.

BACKGROUND: Hypo-magnesemia is described to occur in as many as 65% of intensive care unit (ICU) patients. Magnesium (Mg) is a cofactor in over 300 enzymatic reactions involving energy metabolism, protein, and nucleic acid synthesis. The membrane pump that creates the electrical gradient across the cell membrane is dependent on Mg, and it is important in the activity of electrically excitable tissues. Since Mg regulates the movement of calcium in smooth muscle cells, it is also important in peripheral vascular tone and blood pressure. Studies have linked hypo-magnesemia to multiple chronic diseases and to a higher mortality rate. METHODS: To explore trends within our own tertiary care surgical ICU, we sampled our patients' laboratory records in 2001 and in 2011. Hypo-magnesemia in our ICU is defined as an Mg less than 2.0 mg/dL. RESULTS: This retrospective review of all SICU patients from October to December revealed that there was a significant increase (P < 0.01) in the patients with their serum Mg level measured between 2001 (89%) and 2011 (95%). There was a significant decrease (P < 0.001) in patients with hypomagnesemia (< 2 mg/dL) between 2001 (47.5%) and 2011 (33.0%). On the other hand, there was a significant increase (P < 0.001) in patients with normal serum Mg level (> 2 mg/dL) between 2001 (52.5%) and 2011 (67.0%). CONCLUSIONS: There was not only more monitoring of Mg in 2011, but a lower incidence of hypo-Mg compared to 2001. Possible explanations include changing patterns of antibiotic and diuretic use, less amphotericin use, more frequent laboratory surveillance, and better trained ICU practitioners.

Increasing severity of aortic atherosclerosis in coronary artery bypass grafting patients evaluated by transesophageal echocardiography.

BACKGROUND: Atherosclerotic disease in coronary artery bypass grafting (CABG) patients is a potential contributor to complications in the perioperative periods. This study was undertaken to better define how the frequency of aortic atheromatous disease among patients coming for CABG has evolved over the last decade. METHODS: Data from elective patients coming for CABG who underwent transesophageal echocardiography (TEE) examinations following induction of anesthesia were obtained for the years 2002 and 2009. Aortas were graded according to the method of Kronzon, with the following interpretations: normal = grade I, intimal thickening = 2, atheroma of less than 5 mm = 3, atheroma of > 5 mm = 4, and any mobile atheroma = 5. The data of 124 patients who underwent comprehensive exam of the aorta by one cardiac anesthesiologist were gathered and assigned into two groups based on the year TEE was done. Student's t-test was used for statistical analysis. A P value < 0.05 was considered significant. The data were presented as mean ± SD. RESULTS: There was significant difference between group 2002 (2.05 ± 1.28) and group 2009 (2.59 ± 1.11) in atheroma grade (P = 0.013). CONCLUSIONS: Patients coming for CABG in group 2009 exhibited significantly higher grades of aortic atheroma on TEE, compared to group 2002. Understanding the risk of atheroma in the elderly CABG population may help in altering surgical approaches to lessen the risk of catastrophic stroke. Potential options needing further study include the off-pump approach and modification of cross-clamp site and technique as well as other modalities.

The human visual system uses a global closure mechanism.

Research asserting that the visual system instantiates a global closure heuristic in contour integration has been challenged by an argument that behaviorally-detected closure enhancement could be accounted for by low-level local mechanisms driven by collinearity or "good continuation" interacting with proximity. The present study investigated this issue in three experiments. Exp. 1 compared the visibility of closed and open contours using circles and S-contours from low to moderately high angles of path curvature in a temporal alternative-forced choice task. Circles were more detectable than S-contours, an effect that increased with curvature. The closure enhancement observed can, however, be explained by the fact that circles contain more 'contiguity' than S-contours. Additional tests added discontinuities to otherwise closed paths to control for the effects of good continuation and closure independently. Exp. 2 compared the visibility of incomplete circles (C-contours) and S-contours derived from the full circles and S-contours in Exp. 1. Exp. 3a compared the visibility of arc pairs arranged in an enclosed position similar to "()" and a non-enclosed position similar to ")(". Results consistently showed enhanced visibility of contour configurations enclosing a region even after controlling for differences in contiguity and changes of curvature direction. A control test (Exp. 3b) demonstrated that the gap in the contours of Exp. 3a was too large to be bridged by local-level collinearity/proximity alone. The combination of good continuation and proximity alone does not explain the closure effects observed across these tests, as demonstrated through the application of a Bayesian model of collinearity and proximity (Geisler et al., 2001) to the stimuli in Exps. 3a and 3b. These results argue for the presence of a global closure-driven contour enhancing mechanism in human vision.

Contour integration by 6-month-old infants: discrimination of distinct contour shapes.

Previous research has indicated that the ability to integrate individual elements in the presence of noise is immature in 3-month-old infants. The present study extended the developmental timeline by investigating 6-month-olds' ability to integrate individual elements into whole contours through an assessment of their capability to discriminate circle and square contours constructed from oriented Gabor patches via a newly designed cueing paradigm for infants. If infants discriminate the centrally-presented contour cues, then their eye movements would correctly anticipate subsequent target presentation at a rate greater than chance. The results indicated that infants integrated the contours and discriminated the different shapes, but, consistent with past research, this ability is still fairly immature at this age, tolerating limited amount of noise.

Chronic nitric oxide synthase blockade desensitizes the heart to the negative metabolic effects of nitric oxide.

The consequences of chronic nitric oxide synthase (NOS) blockade on the myocardial metabolic and guanylyl cyclase stimulatory effects of exogenous nitric oxide (NO) were determined. Thirty-three anesthetized open-chest rabbits were randomized into four groups: control, NO donor S-nitroso-N-acetyl-penicillamine (SNAP, 10(-4 )M), NOS blocking agent N(G)-nitro-L-arginine methyl ester (L-NAME, 20 mg/kg/day) for 10 days followed by a 24 hour washout and L-NAME for 10 days followed by a 24 hour washout plus SNAP. Myocardial O(2) consumption was determined from coronary flow (microspheres) and O(2) extraction (microspectrophotometry). Cyclic GMP and guanylyl cyclase activity were determined by radioimmunoassay. There were no baseline metabolic, functional or hemodynamic differences between control and L-NAME treated rabbits. SNAP in controls caused a reduction in O(2) consumption (SNAP 5.9+/-0.6 vs. control 8.4+/-0.8 ml O(2)/min/100 g) and a rise in cyclic GMP (SNAP 18.3+/-3.8 vs. control 10.4+/-0.9 pmol/g). After chronic L-NAME treatment, SNAP caused no significant changes in O(2) consumption (SNAP 7.1+/-0.8 vs. control 6.4+/-0.7) or cyclic GMP (SNAP 14.2+/-1.8 vs. control 12.1+/-1.3). In controls, guanylyl cyclase activity was significantly stimulated by SNAP (216.7+/-20.0 SNAP vs. 34.4+/-2.5 pmol/mg/min base), while this increase was blunted after L-NAME (115.9+/-24.5 SNAP vs. 24.9+/-4.7 base). These results demonstrated that chronic NOS blockade followed by washout blunts the response to exogenous NO, with little effect on cyclic GMP or myocardial O(2) consumption. This was related to reduced guanylyl cyclase activity after chronic L-NAME. These results suggest that, unlike many receptor systems, the NO-cyclic GMP signal transduction system becomes downregulated upon chronic inhibition.

Alterations in ventricular myocyte contraction caused by C-type natriuretic peptide and nitric oxide in eNOS-/- mice.

Lack of endothelial nitric oxide synthase (eNOS) may affect the sensitivity of cyclic GMP signaling through soluble guanylyl cyclase (sGC). We hypothesized that in eNOS knockout (eNOS-/-) mice, stimulation of guanylyl cyclase would have enhanced effects inhibiting cardiac contraction. We measured cell shortening and calcium transients in isolated ventricular myocytes from adult eNOS-/- and wild-type (WT) mice after stimulating particulate guanylyl cyclase (pGC) with C-type natriuretic peptide (CNP, 10(-8) and 10(-7) M) or sGC with S-nitroso-N-acetyl-penicillamine (SNAP, NO donor, 10(-6) and 10(-5) M). Although sGC activity was increased by +71% in eNOS-/-, SNAP had similar effects in the two groups (%shortening -39% control vs. -37% eNOS-/-), suggesting that the cyclic GMP pathway was desensitized in eNOS-/- myocytes. CNP had significantly smaller effects on cell contraction (%shortening -34% control vs. -14% eNOS-/-) and pGC activity was not changed in eNOS-/- myocytes. Similar effects were also produced by guanylin and carbon monoxide, stimulators of pGC and sGC. CNP's effects on Ca(2+) transients were also attenuated in eNOS-/- myocytes. SNAP did not alter Ca(2+) transients in eNOS-/- or control cells. In the eNOS-/- mice, cyclic GMP-dependent protein kinase and cyclic AMP phosphodiesterase activity were reduced. This study demonstrated that the downstream cyclic GMP pathway was attenuated in eNOS-/- mice and this was partially compensated for by increased sGC, but not pGC activity in ventricular myocytes.

Reduction in interaction between cGMP and cAMP in dog ventricular myocytes with hypertrophic failure.

Baseline function and signal transduction are depressed in hearts with hypertrophic failure. We tested the hypothesis that the effects of cGMP and its interaction with cAMP would be reduced in cardiac myocytes from hypertrophic failing hearts. Ventricular myocytes were isolated from control dogs, dogs with aortic valve stenosis hypertrophy, and dogs with pacing hypertrophic failure. Myocyte function was measured using a video edge detector. Cell contraction data were obtained at baseline, with 8-bromo-cGMP (10(-7), 10(-6), and 10(-5) M), with erythro-9-(2-hydroxy-3-nonyl)adenine [EHNA; a cAMP phosphodiesterase (PDE(2)) inhibitor] plus 8-bromo-cGMP, or milrinone (a PDE(3) inhibitor) plus 8-bromo-cGMP. Baseline percent shortening and maximal rates of shortening (R(max)) and relaxation were slightly reduced in hypertrophic myocytes and were significantly lower in failing myocytes (R(max): control dogs, 95.3 +/- 17.3; hypertrophy dogs, 88.2 +/- 5.5; failure dogs, 53.2 +/- 6.4 mum/s). 8-Bromo-cGMP dose dependently reduced myocyte function in all groups. However, EHNA (10(-6) M) and milrinone (10(-6) M) significantly reduced the negative effects of cGMP on cell contractility in control and hypertrophy but not in failing myocytes (R(max) for control dogs: cGMP, -46%; +EHNA, -21%; +milrinone, -19%; for hypertrophy dogs: cGMP, -40%; +EHNA, -13%; +milrinone, -20%; for failure dogs: cGMP, -40%; +EHNA, -29%; +milrinone, -32%). Both combinations of EHNA-cGMP and milrinone-cGMP significantly increased intracellular cAMP in control, hypertrophic, and failing myocytes. These data indicated that the cGMP signaling pathway was preserved in hypertrophic failing cardiac myocytes. However, the interaction of cGMP with the cAMP signaling pathway was impaired in these failing myocytes.

Negative metabolic effects of cGMP are enhanced in obese rat hearts.

Leptin resistance leads to obesity and may affect responses to the second messenger cGMP. We tested the hypothesis that the myocardial negative metabolic response to cGMP would be enhanced in leptin-resistant animals. This hypothesis was tested in anesthetized open-chest Zucker obese (n = 16) and age-matched control rats (n = 13). Coronary blood flow (microspheres) and O2 extraction (microspectrophotometry) measurements were used to determine myocardial O2 consumption (VO2). Protein phosphorylation by cGMP protein kinase and cAMP phosphodiesterase activity were also determined. Either vehicle (saline) or 8-Br-cGMP (10(-3) M) was topically applied to the left ventricular surface. Body weight was significantly greater in the obese rats (523 +/- 17 versus 322 +/- 12 g). There were no hemodynamic differences between groups. There was no difference in VO2 between lean (52 +/- 13 mL O2/min/100 g) and obese (54 +/- 9) vehicle-treated rats. 8-Br-cGMP significantly lowered VO2 in obese (35 +/- 6) but not lean (45 +/- 7) rats. This was not related to altered protein phosphorylation by the cGMP protein kinase. Cyclic GMP inhibited cAMP phosphodiesterase activity in lean but not obese hearts. Thus, the high myocardial oxygen consumption of lean rats was not significantly affected by cGMP but was reduced in obese hearts. This appeared to be related to a reduced inhibition of cAMP phosphodiesterase activity by cGMP in the Zucker obese rat.

Effects of natriuretic peptides on ventricular myocyte contraction and role of cyclic GMP signaling.

Natriuretic peptides, including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) act through different receptors and at different potencies to affect cardiac myocyte function. We tested the hypothesis that these three peptides would differentially reduce cardiomyocyte function through their effects on the cyclic GMP signaling pathway. Rabbit ventricular myocytes were isolated and stimulated by electrical field stimulation. Cell function was measured using a video edge detector. ANP BNP or CNP at 10(-9), 10(-8), 10(-7) M were added to the myocytes. Intracellular cyclic GMP was determined using a radioimmunoassay in the absence or presence of ANP, BNP or CNP. All natriuretic peptides decreased myocyte contractility in a similar concentration dependent manner. Myocyte percentage shortening was significantly decreased with all peptides at 10(-7) M compared with baseline (ANP from 5.4+/-0.4 to 3.9+/-0.2%; BNP from 5.0+/-0.2 to 3.5+/-0.1%; CNP from 5.6+/-0.3 to 4.0+/-0.3%). Maximum rate of shortening and relaxation were also decreased similarly and significantly. Intracellular cyclic GMP was significantly increased in myocytes treated with ANP, BNP or CNP (Baseline 1.0+/-0.2, ANP 2.1+/-0.2, BNP 2.3+/-0.3, CNP 2.0+/-0.2 pmol/10(5) myocytes). Furthermore, inhibition of the cyclic GMP protein kinase with KT5823 caused a reversal in the functional effects of CNP. We concluded that all natriuretic peptides had similar negative effects on ventricular myocyte function and their effects were accompanied by increased cyclic GMP. Blockade the effect of CNP by a cyclic GMP protein kinase inhibitor demonstrated that effects were mediated through the cyclic GMP signaling pathway.

Cyclic GMP signaling and regulation of SERCA activity during cardiac myocyte contraction.

We tested the hypothesis that cGMP-induced reductions in cardiac myocyte function were related to activation of the sarcoplasmic reticulum Ca2+-ATPase (SERCA) and cGMP-dependent phosphorylation of phospholamban. Ventricular myocyte function was measured using a video edge detector (n = 11 rabbits). Thapsigargin (TG) or cyclopiazonic acid (CPA) were used to inhibit SERCA. 8-Bromo-cGMP was added at 10(-6), 10(-5) M followed by TG 10(-8) M or KT5823 (cGMP-protein kinase inhibitor, 10(-6) M) prior to TG or CPA. Cyclic GMP-dependent protein phosphorylation and immunoblotting with anti-phospholamban antibody were examined. TG 10(-8) M significantly increased percent shortening (from 6.6+/-0.7 to 9.1+/-1.3%). Cyclic GMP 10(-5) M significantly decreased cell shortening from 9.3+/-0.9 to 5.1+/-0.6%. This was partially reversed by KT5823 (5.1+/-0.6 to 8.2+/-1.4%) suggesting that negative functional effects of cGMP were partially through the cGMP-dependent protein kinase. Addition of TG after cGMP also reduced the negative effects of cGMP on myocyte shortening suggesting involvement of SERCA in cGMP signaling. TG after cGMP and KT5823 treatment did not alter myocyte contractility (8.2+/-1.4 to 7.2+/-1.3%). CPA had similar effects as those of TG. Protein phosphorylation and immunoblotting showed that phospholamban was a target of the cGMP protein kinase. These results indicated that the cyclic GMP-induced reductions in myocyte function were partially mediated through the action of SERCA. It further suggested that cGMP signaling affects myocyte function through phosphorylation of phospholamban which regulates SERCA activity.