Reduction of death rate due to acute myocardial infarction in subjects with cancers through systemic restoration of impaired nitric oxide.

INTRODUCTION: Excessive aggregation of platelets at the site of plaque rupture on the coronary artery led to the formation of thrombus which is reported to precipitate acute myocardial infarction (AMI). Nitric oxide (NO) has been reported to inhibit platelet aggregation and induce thrombolysis through the in situ formation of plasmin. As the plasma NO level in AMI patients from two different ethnic groups was reduced to 0 µM (median) compared to 4.0 µM (median) in normal controls, the effect of restoration of the NO level to normal ranges on the rate of death due to AMI was determined. METHODS AND RESULTS: The restoration of plasma NO level was achieved by a sticking small cotton pad (10×25 mm) containing 0.28 mmol sodium nitroprusside (SNP) in 0.9% NaCl to the abdominal skin of the participants using non-toxic adhesive tape which was reported to normalize the plasma NO level. The participants (8,283) were volunteers in an independent study who had different kinds of cancers and did not wish to use any conventional therapy for their condition but opted to receive SNP "pad" for their condition for 3 years. The use of SNP "pad" which normalized (≈4.0 µM) the plasma NO level that in consequence reduced the death rate due to AMI, among the participants, was found to be significantly reduced compared to the death due to AMI in normal population. CONCLUSION: Our data suggested that the use of SNP "pad" significantly reduced the death due to AMI. TRIAL REGISTRATION: www.ctri.nic.in CTRI/2013/12/004236

<b>Table-2.</b> Cancer entities of the patients selected for the study.

<p>The study involved the application of SNP “pad” for 3 years in patients suffering from different kinds of cancer. The digits within the parentheses denote the number of patients who volunteered to participate in the present study.</p

Nitric oxide levels in AMI patients in South Asia and in Southern Australia.

<p>The NO level was determined by methemoglobin method as described in the Materials and Methods section in both the cases. Panel A represents the median values of plasma NO level in AMI patients and in the equal number of age and gender matched normal volunteers in Australia. Panel B shows the median values of plasma NO level in AMI patients and in the age and gender matched normal volunteers in India.</p

The age group-plasma NO level adjusted regression model in both Indian and Australian AMI patients.

<p>Regression model of the age related to the plasma NO level in both the Indian and Australian AMI patients was plotted. The age and the corresponding plasma NO level of the participants could be determined from the plot. Solid line represents the regression curve of the age group of the Indian AMI patients. Dotted line indicates the regression curve of the age group of the Australian AMI patients. Solid circles (•) indicate variations in the age group of Indian AMI patients. Solid squares (▪) indicate variations in the age group of the Australian AMI patients. The hollow circles (○) and the hollow squares (□) represent the plasma NO level in Indian and Australian patients respectively.</p

Flowchart representing the participation of the subjects with different cancers who received “antineoplastin” treatment.

<p>Patients with different cancers were selected for the study and “antineoplastin” pad consisting of 0.2 ml of the solution (0.28 mmol of SNP) soaked in a band-aid was applied dermally on the lower abdominal hair-free area as described before <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0088639#pone.0088639-Sinha3" target="_blank">[28]</a>. Please note that the whole process of delivering the “pad” containing “antineoplastin” takes less than 5 min. People from different parts of the world belonging to multi-ethnic and multi-cultural backgrounds have participated in the study including India, Poland, Papua New Guinea, Sri Lanka and Bangladesh. They had used this “antineoplastin” pad for at least a year with a maximum duration of 5 years.</p

Kaplan-Meier model of the survival rate of the animals with ADP induced coronary thrombosis in the presence and absence of the application of dermal SNP “pad”.

<p>To determine the survival rate in the animals from coronary thrombosis by the dermal application of SNP “pad” induced by ADP, Kaplan-Meier survival curve was plotted. Group 1 represents the animals that received the dermal application of SNP “pad”. The curve indicates the survival period which shows survival of the animals up to 72 hours after the repeated injection of ADP. Group 2 represents the control group without SNP “pad” treatment. The survival time of the animals was less than an hour as shown by the curve.</p

Death rates due to acute myocardial infarction in cancer patients with and without the use of SNP “patch” and in the normal counterparts.

a<p>Data cited in Harrison's Principles of Internal Medicine, 16^th Edition, Volume 2, Chapter 208, Approach to the Patient with Cardiovascular Disease by Eugene Braunwald pp 1301, McGraw-Hill Medical Publishing Division.</p>b<p>Data cited in <i>Sinha AK</i>, et al. Neutralization by “<i>antineoplastin</i>” of insulin-activated nitric oxide synthase antibody and its effects in cancers. J Cancer Res Clin Oncol. 2002 Dec;128(12):659–68.</p>c<p>Data cited in Harrison's Principles of Internal Medicine, 16^th Edition, Volume 1, Chapter 66, Approach to the Patient with Cancer by Dan L. Longo pp-435. McGraw-Hill Medical Publishing Division and other journal articles reporting the statistical significance of the occurrence of AMI in cancer patients.</p><p>Sodium Nitroprusside “pad” was prepared and used dermally in patients with different kinds of cancers (n = 8,283) as described in the Materials and Methods in details.</p><p>Death rates due to AMI in the cancer patients who received SNP “pad” for 3 years was compared to the rate of death due to AMI in the normal population as reported in the literature.</p><p>The death rates between the groups were compared by using Z-test, a special case of null hypothesis.</p